Huang X

References (96)

Title : A simple fluorescence detection of acetylcholinesterase with peroxidase-like catalysis from iodide - Huang_2024_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_313_124116
Author(s) : Huang X , Cheng Y , Zhou Q , Tu Y , Yan J
Ref : Spectrochim Acta A Mol Biomol Spectrosc , 313 :124116 , 2024
Abstract : Acetylcholinesterase (AChE) is an important enzyme in the central and peripheral nervous system that regulates the balance of the neurotransmitter acetylcholine. In this work, a simple, selective and sensitive fluorescence assay was developed toward AChE activity. A conventional AChE substrate acetylthiocholine iodide (ATCI) was applied. Instead directly rendering a signaling, it was found that free iodide ions was released during the enzymatic hydrolysis of ATCI. These ions further catalyzed the oxidation of non-emissive o-phenylenediamine (OPD) into a fluorescent product. This gave a response differed from frequently-adopted sulfhydryl- -based signals and thus minimized related interferences. All materials included in this process were directly available and no additional syntheses were required. Due to the extra iodide-based catalysis included, this scheme was capable of providing a sensitive response toward AChE in the range of 0.01-8 U/L, with a limit of detection at 0.006 U/L. This method was further extended onto chlorpyrifos as an exemplary AChE inhibitor, with a detection down to 3 pM.
ESTHER : Huang_2024_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_313_124116
PubMedSearch : Huang_2024_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_313_124116
PubMedID: 38490124

Title : Bacterial lipase-responsive polydopamine nanoparticles for detection and synergistic therapy of wound biofilms infection - Jiang_2024_Int.J.Biol.Macromol__132350
Author(s) : Jiang H , Huang X , Li H , Ren F , Li D , Liu Y , Tong Y , Ran P
Ref : Int J Biol Macromol , :132350 , 2024
Abstract : Wound biofilms represent an elusive conundrum in contemporary treatment and diagnostic options, accredited to their escalating antibiotic resistance and interference in chronic wound healing processes. Here, we developed mesoporous polydopamine (mPDA) nanoparticles, and grafted with rhodamine B (Rb) as biofilm lipase responsive detection probe, followed by Pi - Pi stacking mediated ciprofloxacin (CIP) loading to create mP-Rb@CIP nanoparticles. mPDA NPs with a melanin structure could quench fluorescence emissions of Rb. Once encountering biofilm in vivo, the ester bond in Rb and mPDA is hydrolyzed by elevated lipase concentrations, triggering the liberation of Rb and restore fluorescence emissions to achieve real-time imaging of biofilm-infected wounds. Afterwards, the 808 nm near-infrared (NIR) illumination initiates a spatiotemporal controlled antibacterial photothermal therapy (PTT), boosting its effectiveness through photothermal-triggered CIP release for synergistic biofilm eradication. The mP-Rb@CIP platform exhibits dual diagnostic and therapeutic functions, efficaciously treating biofilm-infected wounds in vivo and in vitro. Particularly, the mP-Rb@CIP/NIR procedure expedites wound-healing by alleviating oxidative stress, modulating inflammatory mediators, boosting collagen synthesis, and promoting angiogenesis. Taken together, the theranostic nanosystem strategy holds significant potential for addressing wound biofilm-associated infections.
ESTHER : Jiang_2024_Int.J.Biol.Macromol__132350
PubMedSearch : Jiang_2024_Int.J.Biol.Macromol__132350
PubMedID: 38750839

Title : Indirubin mediates adverse intestinal reactions in guinea pigs by downregulating the expression of AchE through AhR - Xu_2024_Xenobiotica__1
Author(s) : Xu X , Taha R , Chu C , Xiao L , Wang T , Wang X , Huang X , Jiang Z , Sun L
Ref : Xenobiotica , :1 , 2024
Abstract : Indirubin is the main component of the traditional Chinese medicine Indigo naturalis (IN), a potent agonist of aryl hydrocarbon receptors (AhRs). In China, IN is used to treat psoriasis and ulcerative colitis, and indirubin is used for the treatment of chronic myelogenous leukaemia. However, IN and indirubin have adverse reactions, such as abdominal pain, diarrhoea, and intussusception, and their specific mechanism is unclear.The purpose of our research was to determine the specific mechanism underlying the adverse effects of IN and indirubin. By tracking the modifications in guinea pigs after the intragastric administration of indirubin for 28 days.The results demonstrate that indirubin could accelerate bowel movements and decrease intestinal acetylcholinesterase (AchE) expression. Experiments with NCM460 cells revealed that indirubin significantly reduced the expression of AchE, and the AchE levels were increased after the silencing of AhR and re-exposure to indirubin.This study showed that the inhibition of AchE expression by indirubin plays a key role in the occurrence of adverse reactions to indirubin and that the underlying mechanism is related to AhR-mediated AchE downregulation.
ESTHER : Xu_2024_Xenobiotica__1
PubMedSearch : Xu_2024_Xenobiotica__1
PubMedID: 38164702

Title : Two Fluorescent Probes for Recognition of Acetylcholinesterase: Design, Synthesis, and Comparative Evaluation - Lin_2024_Molecules_29_
Author(s) : Lin X , Yi Q , Qing B , Lan W , Jiang F , Lai Z , Huang J , Liu Q , Jiang J , Wang M , Zou L , Huang X , Wang J
Ref : Molecules , 29 : , 2024
Abstract : In this study, two "on-off" probes (BF(2)-cur-Ben and BF(2)-cur-But) recognizing acetylcholinesterase (AChE) were designed and synthesized. The obtained probes can achieve recognition of AChE with good selectivity and pH-independence with a linear range of 0.5~7 U/mL and 0.5~25 U/mL respectively. BF(2)-cur-Ben has a lower limit of detection (LOD) (0.031 U/mL), higher enzyme affinity (K(m) = 16 +/- 1.6 microM), and higher inhibitor sensitivity. A responsive mechanism of the probes for AChE was proposed based on HPLC and mass spectra (MS) experiments, as well as calculations. In molecular simulation, BF(2)-cur-Ben forms more hydrogen bonds (seven, while BF(2)-cur-But has only four) and thus has a more stable enzyme affinity, which is mirrored by the results of the comparison of K(m) values. These two probes could enable recognition of intracellular AChE and probe BF(2)-cur-Ben has superior cell membrane penetration due to its higher log p value. These probes can monitor the overexpression of AChE during apoptosis of lung cancer cells. The ability of BF(2)-cur-Ben to monitor AChE in vivo was confirmed by a zebrafish experiment.
ESTHER : Lin_2024_Molecules_29_
PubMedSearch : Lin_2024_Molecules_29_
PubMedID: 38731452

Title : Complete genome sequencing of Hortaea werneckii M-3 for identifying polyester polyurethane degrading enzymes - Ling_2024_Mar.Genomics_75_101111
Author(s) : Ling M , Zhang K , Hu J , Huang X , Fan G , Grossart HP , Luo Z
Ref : Mar Genomics , 75 :101111 , 2024
Abstract : Hortaea werneckii M-3, a black yeast isolated from the marine sediment of the West Pacific, can utilize polyester polyurethane (PU, Impranil DLN) as a sole carbon source. Here, we present the complete genome of Hortaea werneckii M-3 with the focus on PU degradation enzymes. The total genome size is 38,167,921 bp, consisting of 186 contigs with a N50 length of 651,266 bp and a GC content of 53.06%. Genome annotation analysis predicts a total of 13,462 coding genes, which include 99 tRNAs and 105 rRNAs. Some genes encoding PU degrading enzymes including cutinase and urease are identified in this genome. The genome analysis of Hortaea werneckii M-3 will be helpful for further understanding the degradation mechanism of polyester PU by marine yeasts.
ESTHER : Ling_2024_Mar.Genomics_75_101111
PubMedSearch : Ling_2024_Mar.Genomics_75_101111
PubMedID: 38735674

Title : Smartphone-based colorimetric sensor array using gold nanoparticles for rapid distinguishment of multiple pesticides in real samples - Zhao_2023_Food.Chem_404_134768
Author(s) : Zhao T , Liang X , Guo X , Yang X , Guo J , Zhou X , Huang X , Zhang W , Wang Y , Liu Z , Jiang Z , Zhou H
Ref : Food Chem , 404 :134768 , 2023
Abstract : A simple, sensitive method for pesticide distinguishment based on a colorimetric sensor array using diverse gold nanoparticles (AuNPs) at room temperature is presented in this study. Acetylcholinesterase (AChE) hydrolysis ability was influenced by different pesticides and produced different concentrations of thiocholine by hydrolyzing acetylthiocholine iodide (ATCh). Thiocholine could be easily linked to the AuNPs through an Aus-sS covalent bond, and AuNPs underwent aggregation, resulting in a visible color change due to alteration of surface plasmon resonance properties. Based on these results, we successfully distinguished eight pesticides (glyphosate, thiram, imidacloprid, tribenuron methyl, nicosulfuron, thifensulfuron methyl, dichlorprop, and fenoprop) utilizing five different AuNPs by colorimetric assay. The limit of detection (LOD) of this visual method for all pesticides was less than 1.5x 10(-7) M, which was more sensitive than the U.S. Environmental Protection Agency regulations specify (1.18s-s3.91x10(-6) M). This method was further improved by combining a portable smartphone device with a color picking application using (color name AR) and RGB (red, green, blue) values. The method was successfully applied to pesticide residue distinguishment in real samples by linear discriminant analysis (LDA).
ESTHER : Zhao_2023_Food.Chem_404_134768
PubMedSearch : Zhao_2023_Food.Chem_404_134768
PubMedID: 36444090

Title : Crystal structures of herbicide-detoxifying esterase reveal a lid loop affecting substrate binding and activity - Liu_2023_Nat.Commun_14_4343
Author(s) : Liu B , Wang W , Qiu J , Huang X , Qiu S , Bao Y , Xu S , Ruan L , Ran T , He J
Ref : Nat Commun , 14 :4343 , 2023
Abstract : SulE, an esterase, which detoxifies a variety of sulfonylurea herbicides through de-esterification, provides an attractive approach to remove environmental sulfonylurea herbicides and develop herbicide-tolerant crops. Here, we determined the crystal structures of SulE and an activity improved mutant P44R. Structural analysis revealed that SulE is a dimer with spacious binding pocket accommodating the large sulfonylureas substrate. Particularly, SulE contains a protruding beta hairpin with a lid loop covering the active site of the other subunit of the dimer. The lid loop participates in substrate recognition and binding. P44R mutation altered the lid loop flexibility, resulting in the sulfonylurea heterocyclic ring repositioning to a relative stable conformation thus leading to dramatically increased activity. Our work provides important insights into the molecular mechanism of SulE, and establish a solid foundation for further improving the enzyme activity to various sulfonylurea herbicides through rational design.
ESTHER : Liu_2023_Nat.Commun_14_4343
PubMedSearch : Liu_2023_Nat.Commun_14_4343
PubMedID: 37468532
Gene_locus related to this paper: 9rhiz-g9i933

Title : Ultrahigh-Throughput Directed Evolution of Polymer-Degrading Enzymes Using Yeast Display - Cribari_2023_J.Am.Chem.Soc__
Author(s) : Cribari MA , Unger MJ , Unarta IC , Ogorek AN , Huang X , Martell JD
Ref : Journal of the American Chemical Society , : , 2023
Abstract : Enzymes that degrade synthetic polymers have attracted intense interest for eco-friendly plastic recycling. However, because enzymes did not evolve for the cleavage of abiotic polymers, directed evolution strategies are needed to enhance activity for plastic degradation. Previous directed evolution efforts relied on polymer degradation assays that were limited to screening -10(4) mutants. Here, we report a high-throughput yeast surface display platform to rapidly evaluate >10(7) enzyme mutants for increased activity in cleaving synthetic polymers. In this platform, individual yeast cells display distinct mutants, and enzyme activity is detected by a change in fluorescence upon the cleavage of a synthetic probe resembling a polymer of interest. Highly active mutants are isolated by fluorescence activated cell sorting and identified through DNA sequencing. To demonstrate this platform, we performed directed evolution of a polyethylene terephthalate (PET)-depolymerizing enzyme, leaf and branch compost cutinase (LCC). We identified activity-boosting mutations that substantially increased the kinetics of degradation of solid PET films. Biochemical assays and molecular dynamics (MD) simulations of the most active variants suggest that the H218Y mutation improves the binding of the enzyme to PET. Overall, this evolution platform increases the screening throughput of polymer-degrading enzymes by 3 orders of magnitude and identifies mutations that enhance kinetics for depolymerizing solid substrates.
ESTHER : Cribari_2023_J.Am.Chem.Soc__
PubMedSearch : Cribari_2023_J.Am.Chem.Soc__
PubMedID: 38051911
Gene_locus related to this paper: 9bact-g9by57

Title : Polyphenols: Natural food grade biomolecules for treating neurodegenerative diseases from a multi-target perspective - Li_2023_Front.Nutr_10_1139558
Author(s) : Li Z , Zhao T , Shi M , Wei Y , Huang X , Shen J , Zhang X , Xie Z , Huang P , Yuan K , Li N , Qin D
Ref : Front Nutr , 10 :1139558 , 2023
Abstract : As natural functional bioactive ingredients found in foods and plants, polyphenols play various antioxidant and anti-inflammatory roles to prevent the development of disease and restore human health. The multi-target modulation of polyphenols provides a novel practical therapeutic strategy for neurodegenerative diseases that are difficult to treat with traditional drugs like glutathione and cholinesterase inhibitors. This review mainly focuses on the efficacy of polyphenols on ischemic stroke, Parkinson's disease and Alzheimer's disease, including in vivo and in vitro experimental studies. It is further emphasized that polyphenols exert neuroprotective effects primarily through inhibiting production of oxidative stress and inflammatory cytokines, which may be the underlying mechanism. However, polyphenols are still rarely used as medicines to treat neurodegenerative diseases. Due to the lack of clinical trials, the mechanism of polyphenols is still in the stage of insufficient exploration. Future large-scale multi-center randomized controlled trials and in-depth mechanism studies are still needed to fully assess the safety, efficacy and side effects of polyphenols.
ESTHER : Li_2023_Front.Nutr_10_1139558
PubMedSearch : Li_2023_Front.Nutr_10_1139558
PubMedID: 36925964

Title : The preferential utilization of hepatic glycogen as energy substrates in largemouth bass (Micropterus salmoides) under short-term starvation - Zhang_2023_Fish.Physiol.Biochem__
Author(s) : Zhang N , Wang X , Han Z , Gong Y , Huang X , Chen N , Li S
Ref : Fish Physiol Biochem , : , 2023
Abstract : To elucidate the underlying mechanism of the energy metabolism in largemouth bass (Micropterus salmoides), cultured fish (initial body weight: 77.57 +/- 0.75 g) in the present study were starved for 0 h, 12 h, 24 h, 48 h, 96 h and 192 h, respectively. The proximate composition analysis showed that short-term starvation induced a significant up-regulation in crude protein proportion in hepatic of cultured fish (P < 0.05). However, short-term starvation significantly decreased the hepatosomatic index and the viscerosomatic index of cultured fish (P < 0.05). The exact hepatic glycogen content in the group starved for 92 h presented remarkable decrease (P < 0.05). Meanwhile, compared with the weight change of lipid and protein (mg) in hepatic (y = 0.0007x(2) - 0.2827x + 49.402; y = 0.0013x(2) - 0.5666x + 165.31), the decreasing trend of weight in glycogen (mg) was more pronounced (y = 0.0032x(2) - 1.817x + 326.52), which suggested the preferential utilization of hepatic glycogen as energy substrates under short-term starvation. Gene expression analysis revealed that the starvation down-regulated the expression of insulin-like growth factor 1 and genes of TOR pathway, such as target of rapamycin (tor) and ribosomal protein S6 (s6) (P < 0.05). In addition, the starvation significantly enhanced expression of lipolysis-related genes, including hormone-sensitive lipase (hsl) and carnitine palmitoyl transferase I (cpt1), but down-regulated lipogenesis as indicated by the inhibited expression of fatty acids synthase (fas), acetyl-CoA carboxylase 1 (acc1) and acetyl-CoA carboxylase 2 (acc2) (P < 0.05). Starvation of 24 h up-regulated the expression of glycolysis genes, glucokinase (gk), phosphofructokinase liver type (pfkl) and pyruvate kinase (pk), and then their expression returned to the normal level. Meanwhile, the expression of gluconeogenesis genes, such as glucose-6-phosphatase catalytic subunit (g6pc), fructose-1,6-bisphosphatase-1 (fbp1) and phosphoenolpyruvate carboxy kinase (pepck), was significantly inhibited with the short-term starvation (P < 0.05). In conclusion, short-term starvation induced an overall decline in growth performance, but it could deplete the hepatic glycogen accumulation and mobilize glycogen for energy effectively.
ESTHER : Zhang_2023_Fish.Physiol.Biochem__
PubMedSearch : Zhang_2023_Fish.Physiol.Biochem__
PubMedID: 38108936

Title : Dual-mode colorimetric-photothermal sensing platform of acetylcholinesterase activity based on the peroxidase-like activity of Fe-N-C nanozyme - Lu_2022_Anal.Chim.Acta_1229_340383
Author(s) : Lu L , Hu X , Zeng R , Lin Q , Huang X , Li M , Tang D
Ref : Anal Chim Acta , 1229 :340383 , 2022
Abstract : Sensors based on colorimetry, fluorescence, and electrochemistry have been widely employed to detect acetylcholinesterase and its inhibitors, however, there are only a minority of strategies for AChE detection based on photothermal method. This work reports a versatile dual-mode colorimetric and photothermal biosensing platform for acetylcholinesterase (AChE) detection and its inhibitor (paraoxon-ethyl, a model of AChE inhibitors) monitor based on Fe-N-C/H(2)O(2)/3,3',5,5'-tetramethylbenzidine (TMB) system. The Fe-N-C with abundant active Fe-Nx sites shows outstanding peroxidase-mimicking activity and can be used to promote the generation of OH by H(2)O(2) to oxidize TMB. However, the introduction of mercapto molecules tending to coordinate with metal atoms result in the block of action site in Fe-N-C, thereby decrease its peroxidase-mimetic activity. The designed biosensor principle is based on the block of active sites of Fe-N-C by thiocholine (TCh, one kind of mercapto molecules) that can be produced by acetylthiocholine (ATCh) in the presence of AChE. Under optimum conditions, the limit of detection (LOD) for AChE activity is 1.9 mU mL(-1) (colorimetric) and 2.2 mU mL(-1) (photothermal), while for paraoxon-ethyl is 0.012 microg mL(-1) (colorimetric) and 0.013 microg mL(-1) (photothermal), respectively. The assay we proposed not only can be designed to monitor AChE detection and its inhibitors, but also can be easily extended for the detection of other biomolecules relate to the generation or consumption of H(2)O(2).
ESTHER : Lu_2022_Anal.Chim.Acta_1229_340383
PubMedSearch : Lu_2022_Anal.Chim.Acta_1229_340383
PubMedID: 36156227

Title : Maternal Low-Protein Diet during Puberty and Adulthood Aggravates Lipid Metabolism of Their Offspring Fed a High-Fat Diet in Mice - Huang_2022_Nutrients_14_
Author(s) : Huang X , Zhuo Y , Jiang D , Zhu Y , Fang Z , Che L , Lin Y , Xu S , Hua L , Zou Y , Huang C , Li L , Wu D , Feng B
Ref : Nutrients , 14 : , 2022
Abstract : A maternal low-protein (LP) diet during gestation and/or lactation results in metabolic syndrome in their offspring. Here, we investigated the effect of maternal LP diet during puberty and adulthood on the metabolic homeostasis of glucose and lipids in offspring. Female mice were fed with normal-protein (NP) diet or a LP diet for 11 weeks. Male offspring were then fed with a high-fat diet (NP-HFD and LP-HFD groups) or standard chow diet (NP-Chow and LP-Chow groups) for 4 months. Results showed that maternal LP diet during puberty and adulthood did not alter the insulin sensitivity and hepatic lipid homeostasis of their offspring under chow diet, but aggravated insulin resistance, hepatic steatosis, and hypercholesterolemia of offspring in response to a post-weaning HFD. Accordingly, transcriptomics study with offspring's liver indicated that several genes related to glucose and lipid metabolism, including lipoprotein lipase (Lpl), long-chain acyl-CoA synthetase 1 (Acsl1), Apoprotein A1 (Apoa1), major urinary protein 19 (Mup19), cholesterol 7alpha hydroxylase (Cyp7a1) and fibroblast growth factor 1 (Fgf1), were changed by maternal LP diet. Taken together, maternal LP diet during puberty and adulthood could disarrange the expression of metabolic genes in the liver of offspring and aggravate insulin resistance and hepatic steatosis in offspring fed a HFD.
ESTHER : Huang_2022_Nutrients_14_
PubMedSearch : Huang_2022_Nutrients_14_
PubMedID: 36235710

Title : Structure-guided rational design of the Geobacillus thermoglucosidasius feruloyl esterase GthFAE to improve its thermostability - Yang_2022_Biochem.Biophys.Res.Commun_600_117
Author(s) : Yang W , Sun L , Dong P , Chen Y , Zhang H , Huang X , Wu L , Chen L , Jing D , Wu Y
Ref : Biochemical & Biophysical Research Communications , 600 :117 , 2022
Abstract : Feruloyl esterases are indispensable biocatalysts catalyzing the cleavage of ester bonds between polysaccharides and their hydroxycinnamoyl cross-links. GthFAE from Geobacillus thermoglucosidasius was identified as a thermophilic alkaline feruloyl esterase with potential applications in paper manufacturing. To improve the enzymatic properties rationally and efficiently, the structure of GthFAE was solved at 1.9 A, revealing a core domain of classical alpha/beta hydrolase fold and an inserted alpha/beta cap domain. In silico analysis based on it helped us to investigate whether the residues at the active center have positive effects on the stability, and how. Several site-directed mutations were conducted, of which substitutions at residues T41 and T150 apparently improved the thermostability. The combination mutant T41N/T150R exhibited an optimal temperature of 65 degreesC, a 6.4 degreesC higher T(m) compared to wild type by 80 degreesC, and a 35-fold longer in half-life (201 min) at 70 degreesC. Molecular dynamics simulations further illustrated that the structure of T41N/T150R was more stable than the wild type and T150R stabilized the cap domain by introducing salt bridges to the region with E154 and D164. This study not only highlighted residues within the active center on their thermostability improving effects, but also contributed to the prospective industrial application of GthFAE.
ESTHER : Yang_2022_Biochem.Biophys.Res.Commun_600_117
PubMedSearch : Yang_2022_Biochem.Biophys.Res.Commun_600_117
PubMedID: 35219099
Gene_locus related to this paper: partm-GthFAE

Title : The role of butyrylcholinesterase in the regulation of cognitive dysfunction in minimal hepatic encephalopathy: A potential blood marker of disease evolution - Yang_2022_Front.Neurol_13_900997
Author(s) : Yang X , Dang P , Liu W , Ma W , Ge X , Zhu K , Wang M , Huang X , Ding X , Wang X
Ref : Front Neurol , 13 :900997 , 2022
Abstract : BACKGROUND AND AIMS: Patients with cirrhosis commonly experience minimal hepatic encephalopathy (MHE), and alterations in neurotransmitters have been thought to be related to cognitive function. However, the relationship between alterations in peripheral and central butyrylcholinesterase (BuChE) with MHE disease progression remains unknown. As such, this study was designed to investigate potential changes in peripheral and central BuChE activity and their effects on cognitive function in the context of MHE. MATERIALS AND METHODS: We enrolled 43 patients with cirrhosis secondary to hepatitis B, 20 without MHE and 23 with MHE, and 25 with healthy controls (HC). All the selected subjects underwent resting-state functional MRI, and the original images were processed to obtain the regional homogeneity (ReHo) brain maps. Thereafter, the correlation of BuChE activity with ReHo, number connection test of type A (NCT-A), and digital symbol test (DST) scores with MHE patients were analyzed using Person correlation analysis. Meanwhile, we purchased 12 Sprague-Dawley (SD) rats and divided them into an experimental group (n = 6) and a control group (n = 6). The rats in the experimental group were intraperitoneally injected with thioacetamide (TAA) to prepare MHE model rats. After modeling, we used the Morris water maze (MWM) and elevated plus maze (EPM) to assess the cognition function and exploratory behavior of all rats. The activity of serum, hippocampus, and frontal lobe tissue BuChE was detected by ELISA. RESULTS: BuChE activity gradually decreased among the HC, patients with cirrhosis, and MHE groups (all P < 0.01). We observed a linear correlation between serum BuChE and NCT-A and DST scores in MHE patients (all P < 0.01). We noted that BuChE activity can negatively correlate with ReHo values in the left middle temporal gyrus and left inferior temporal gyrus, and positively correlate with ReHo values in the right inferior frontal gyrus, and also found that the peripheral BuChE activity of MHE rats was significantly lower than their control counterparts, and the BuChE activity in frontal lobe extracts was significantly higher than the control rats (all P < 0.05). CONCLUSION: The altered activity of BuChE may contribute to cognitive impairment in MHE patients, which may be a potential biomarker of disease evolution in the context of MHE.
ESTHER : Yang_2022_Front.Neurol_13_900997
PubMedSearch : Yang_2022_Front.Neurol_13_900997
PubMedID: 36341087

Title : Late onset of neutral lipid storage disease due to a rare PNPLA2 mutation in a patient with myopathy and cardiomyopathy -
Author(s) : Tian Y , Wang S , Wang F , Yi L , Dong M , Huang X
Ref : Chinese Medical Journal (Engl) , 135 :2389 , 2022
PubMedID: 36535014

Title : Biodegradation of diphenyl ether herbicide lactofen by Bacillus sp. YS-1 and characterization of two initial degrading esterases - Shang_2022_Sci.Total.Environ_806_151357
Author(s) : Shang N , Chen L , Cheng M , Tian Y , Huang X
Ref : Sci Total Environ , 806 :151357 , 2022
Abstract : The extensive use of the diphenyl ether herbicide lactofen in recent years has caused serious environmental problems. Therefore, detoxification and elimination of lactofen from the environment are urgently required. In this study, the lactofen-degrading strain Bacillus sp. YS-1 was isolated, which achieved a 97.6% degradation rate of 50 mg/L lactofen within 15 h. The ester bond of lactofen was hydrolyzed, which generated acifluorfen, and then, the nitro group was reduced to the amino group, which generated aminoacifluorfen. Finally, the amino group was acetylated, which formed acetylated aminoacifluorfen, a novel end product in the degradation of lactofen. The toxicity of acetylated aminoacifluorfen to the root and seedling growth of cucumber and sorghum was significantly decreased compared with that of lactofen. The two esterase genes rhoE and rapE, encoding two esterases responsible for lactofen hydrolysis to acifluorfen, were cloned and expressed. The amino acid sequences encoded by rhoE and rapE were 27.78% and 88.21% identical with known esterases, respectively. The optimum temperatures for RhoE and RapE degradation of lactofen were 35 degreesC and 25 degreesC, respectively, and both esterases displayed maximal activity at pH 8.0. Both RhoE and RapE prioritized the degradation of (S)-(+)-lactofen, (S)-(-)-quizalofop-ethyl, and (S)-(-)-diclofop-methyl. This study provided the resources of bacterial strain and hydrolyzing enzyme for the removal of lactofen from the environment and the bioremediation of herbicide-contaminated soil.
ESTHER : Shang_2022_Sci.Total.Environ_806_151357
PubMedSearch : Shang_2022_Sci.Total.Environ_806_151357
PubMedID: 34742792
Gene_locus related to this paper: bacsp-a0a6b9cu04 , 9baci-a0a0d7fsc6

Title : A narrative review: The pharmaceutical evolution of phenolic syringaldehyde - Wu_2022_Biomed.Pharmacother_153_113339
Author(s) : Wu J , Fu YS , Lin K , Huang X , Chen YJ , Lai D , Kang N , Huang L , Weng CF
Ref : Biomed Pharmacother , 153 :113339 , 2022
Abstract : To better understand the pharmacological characters of syringaldehyde (SA), which is a key-odorant compound of whisky and brandy, this review article is the first to compile the published literature for molecular docking that were subsequently validated by in vitro and in vivo assays to predict and develop insights into the medicinal properties of SA in terms of anti-oxidation, anti-inflammation, and anti-diabetes. The molecular docking displayed significantly binding affinity for SA towards tumor necrosis factor-alpha, interleukin-6, and antioxidant enzymes when inflammation from myocardial infarction and spinal cord ischemia. Moreover, SA nicely docked with dipeptidyl peptidase-IV, glucagon-like peptide 1 receptor, peroxisome proliferator-activated receptor, acetylcholine M2 receptor, and acetylcholinesterase in anti-diabetes investigations. These are associated with (1) an increase glucose utilization and insulin sensitivity to an anti-hyperglycemic effect; and (2) to potentiate intestinal contractility to abolish the alpha-amylase reaction when concurrently reducing retention time and glucose absorption of the intestinal tract to achieve a glucose-lowering effect. In silico screening of multi-targets concomitantly with preclinical tests could provide a potential exploration for new indications for drug discovery and development.
ESTHER : Wu_2022_Biomed.Pharmacother_153_113339
PubMedSearch : Wu_2022_Biomed.Pharmacother_153_113339
PubMedID: 35780614

Title : Insecticidal Activity of a Component, (-)-4-Terpineol, Isolated from the Essential Oil of Artemisia lavandulaefolia DC. against Plutella xylostella (L.) - Huang_2022_Insects_13_
Author(s) : Huang X , Du L , Liu T , Ma R , Liu X , Yuan H , Liu S
Ref : Insects , 13 : , 2022
Abstract : Plutella xylostella (L.) is one of the most serious pests of cruciferous vegetables. Our previous work demonstrated that the essential oil of Artemisia lavandulaefolia DC. exhibits promising insecticidal activities against P. xylostella. This study further characterizes the key components that are responsible for the insecticidal effect. In total, 47 compounds (96.52% of the total compounds) were identified from the total oil using GC-MS, and the major compounds were eucalyptol (21.57%), D(+)-camphor (17.33%), (-)-4-terpineol (9.96%) and caryophyllene oxide (10.96%). Among them, (-)-4-terpineol showed significantly larvicidal and fumigant activities against P. xylostella. The LD(50) of (-)-4-terpineol was 43.15 mg/mL at 12 h and 31.22 mg/mL at 24 h for 3rd instar larvae, and the LC(50) for adults was 8.34 mg/mL at 12 h and 7.35 mg/mL at 24 h. In addition, the adults treated with (-)-4-terpineol showed varying degrees of inhibitory activity toward glutathione S-transferase, catalase, acetylcholinesterase and Na(+)/K(+)-ATPase at different post-treatment intervals and concentrations. The results indicate that (-)-4-terpineol has promising insecticidal activities against P. xylostella, and it has good inhibitory effects on the four enzymes of P. xylostella adults.
ESTHER : Huang_2022_Insects_13_
PubMedSearch : Huang_2022_Insects_13_
PubMedID: 36555036

Title : An RDH-Plin2 axis modulates lipid droplet size by antagonizing Bmm lipase - Zhao_2022_EMBO.Rep__e52669
Author(s) : Zhao X , Wang W , Yao Y , Li X , Huang X , Wang Y , Ding M
Ref : EMBO Rep , :e52669 , 2022
Abstract : The size of lipid droplets varies greatly in vivo and is determined by both intrinsic and extrinsic factors. From an RNAi screen in Drosophila, we found that knocking down subunits of COP9 signalosome (CSN) results in enlarged lipid droplets under high-fat, but not normal, conditions. We identified CG2064, a retinol dehydrogenase (RDH) homolog, as the proteasomal degradation target of CSN in regulating lipid droplet size. RDH/CG2064 interacts with the lipid droplet-resident protein Plin2 and the RDH/CG2064-Plin2 axis acts to reduce the overall level and lipid droplet localization of Bmm/ATGL lipase. This axis is important for larval survival under prolonged starvation. Thus, we discovered an RDH-Plin2 axis modulates lipid droplet size.
ESTHER : Zhao_2022_EMBO.Rep__e52669
PubMedSearch : Zhao_2022_EMBO.Rep__e52669
PubMedID: 35132760

Title : EZH2-mediated lncRNA ABHD11-AS1 promoter regulates the progression of ovarian cancer by targeting miR-133a-3p - Zhang_2021_Anticancer.Drugs_32_269
Author(s) : Zhang W , Huang X , Shi J
Ref : Anticancer Drugs , 32 :269 , 2021
Abstract : Long-chain noncoding RNAs (lncRNAs) are involved in a wide range of biological and pathological processes in ovarian cancer. The purpose of this study was to investigate the effects of EZH2-mediated ABHD11-AS1 promoter on the pathogenesis of ovarian cancer. The expression levels of EZH2, ABHD11-AS1 and miR-133a-3p were examined in ovarian cancer tissues using reverse transcription-quantitative PCR. Cell proliferation was evaluated using cell counting kit 8 assay, and cell invasion/migration was determined using a Transwell assay. Cell apoptosis was evaluated using flow cytometry. Dual luciferase assay was performed to confirm the interaction between ABHD11-AS1 and miR-133a-3p. The binding site of H3K27me3 on ABHD11-AS1 promoter was confirmed by ChIP. The expression of ABHD11-AS1 was significantly upregulated in ovarian cancer samples, and its levels were closely associated with lymph node metastasis, tumor stage and 3-year survival rate. Furthermore, interference of ABHD11-AS1 suppressed the proliferation, migration and invasion of ovarian cancer cells, while cell apoptosis was promoted. Additionally, miR-133a-3p could be a novel target of ABHD11-AS1, and EZH2-mediated H3K27me3 protein might bind to ABHD11-AS1 promoter directly. Moreover, rescue experiments indicated that the effects caused by ABHD11-AS1 knockdown on the malignant characteristics of ovarian cancer cells were notably enhanced by miR-133a-3p mimics, whereas the influences on cell growth and metastasis induced by overexpressed ABHD11-AS1 were abrogated by the restoration of miR-133a-3p expression. In summary, EZH2-mediated enrichment of H3K27me3 on ABHD11-AS1 promoter could regulate the progression of ovarian cancer via miR-133a-3p. Therefore, EZH2/ABHD11-AS1/miR-133a-3p axis might be a putative candidate for targeted treatment of ovarian cancer.
ESTHER : Zhang_2021_Anticancer.Drugs_32_269
PubMedSearch : Zhang_2021_Anticancer.Drugs_32_269
PubMedID: 33491971
Gene_locus related to this paper: human-ABHD11

Title : Isolation and Insecticidal Activity of Essential Oil from Artemisia lavandulaefolia DC. against Plutella xylostella - Huang_2021_Toxins.(Basel)_13_
Author(s) : Huang X , Huang Y , Yang C , Liu T , Liu X , Yuan H
Ref : Toxins (Basel) , 13 : , 2021
Abstract : Many plants show significant biological activity against pests due to their unique chemical constituents. It is important to identify effective constituents for their development and utilization as botanical pesticides. Our previous study showed that Artemisia lavandulaefolia essential oil had biological activity against Plutella xylostella. Here, we isolated and identified the constituents of essential oil from A. lavandulaefolia by silica gel column chromatography. The main constituents identified were eucalyptol and caryophyllene oxide, and they were confirmed by gas chromatography-mass spectrometry (GC-MS). Eucalyptol and caryophyllene oxide showed strong contact toxicity against P. xylostella larvae after 24 h of application (Median lethal dose, LD(50) = 76.97 microL/mL and 20.71 mg/mL. Furthermore, the two active constituents against P. xylostella adults showed significant fumigant activity (Mmedian lethal concentration, LC(50) = 3.25 microL/L and 1.06 mg/L, respectively. Finally, we measured the detoxification enzymes and acetylcholinesterase of the larvae treated with active constituents. The eucalyptol-treated larvae displayed enhanced carboxylesterase (CarE) and glutathione-S-transferase (GST) activities in an in vivo experiment, but it was lower for acetylcholinesterase (AchE) activity. The activities of the CarE and GST significantly decreased when exposed to caryophyllene oxide. In general, the two active constituents, eucalyptol and caryophyllene oxide, showed high insecticidal activity, which demonstrates their potential to be used as natural insecticides.
ESTHER : Huang_2021_Toxins.(Basel)_13_
PubMedSearch : Huang_2021_Toxins.(Basel)_13_
PubMedID: 34941680

Title : Design and synthesis of novel tacrine-dipicolylamine dimers that are multiple-target-directed ligands with potential to treat Alzheimer's disease - Zhang_2021_Bioorg.Chem_116_105387
Author(s) : Zhang P , Wang Z , Mou C , Zou J , Xie Y , Liu Z , Benjamin Naman C , Mao Y , Wei J , Huang X , Dong J , Yang M , Wang N , Jin H , Liu F , Lin D , Liu H , Zhou F , He S , Zhang B , Cui W
Ref : Bioorg Chem , 116 :105387 , 2021
Abstract : Alzheimer's disease (AD) is a prevalent neurodegenerative disorder that has multiple causes. Therefore, multiple-target-directed ligands (MTDLs), which act on multiple targets, have been developed as a novel strategy for AD therapy. In this study, novel drug candidates were designed and synthesized by the covalent linkings of tacrine, a previously used anti-AD acetylcholinesterase (AChE) inhibitor, and dipicolylamine, an beta-amyloid (Abeta) aggregation inhibitor. Most tacrine-dipicolylamine dimers potently inhibited AChE and Abeta(1-42) aggregation in vitro, and 13a exhibited nanomolar level inhibition. Molecular docking analysis suggested that 13a could interact with the catalytic active sites and the peripheral anion site of AChE, and bind to Abeta(1-42) pentamers. Moreover, 13a effectively attenuated Abeta(1-42) oligomers-induced cognitive dysfunction in mice by activating the cAMP-response element binding protein/brain-derived neurotrophic factor signaling pathway, decreasing tau phosphorylation, preventing synaptic toxicity, and inhibiting neuroinflammation. The safety profile of 13a in mice was demonstrated by acute toxicity experiments. All these results suggested that novel tacrine-dipicolylamine dimers, especially 13a, have multi-target neuroprotective and cognitive-enhancing potentials, and therefore might be developed as MTDLs to combat AD.
ESTHER : Zhang_2021_Bioorg.Chem_116_105387
PubMedSearch : Zhang_2021_Bioorg.Chem_116_105387
PubMedID: 34628225

Title : 3D-Printed, Portable, Fluorescent-Sensing Platform for Smartphone-Capable Detection of Organophosphorus Residue Using Reaction-Based Aggregation Induced Emission Luminogens - Jiao_2021_ACS.Sens__
Author(s) : Jiao Z , Guo Z , Huang X , Yang J , Huang J , Liu Y , Liu G , Zhang P , Song C , Tang BZ
Ref : ACS Sens , : , 2021
Abstract : Development of an easy-to-use, low-cost, household device can help the consumer quickly identify an organophosphorus (OP) residue concentration level. In this work, we demonstrate a 3D-printed, portable, fluorescent-sensing platform for smartphone-capable detection of OPs in vegetables. For development of the proposed device, we utilize the smartphone for capturing the strong thiol-activated fluorescence, which was produced by hydrolysis of OPs in the presence of alkali. The thiol-responsive AIEgen (maleimide-functionalized tetraphenylethylene) was non-emissive in both solution and the solid state but could be readily lighted up by the click addition of thiol to its MI pendant. An android application "Detection" has been developed on the basis of the gray value to analyze the different concentration levels of OPs in vegetable samples. The gray value was linearly related with the concentration of five kinds of organophosphorus residue, ranging from 0 to 20 microg/mL. It was also applied for determination of OPs residue in the leaves of cowpea, celery, and Chinese cabbage. Different from acetylcholinesterase enzyme-based sensors for poor stability under high temperature, the proposed method was a direct detection method for OPs and can be used for rapid monitoring of OPs residue concentration levels before LC-MS analysis.
ESTHER : Jiao_2021_ACS.Sens__
PubMedSearch : Jiao_2021_ACS.Sens__
PubMedID: 34406746

Title : Identification and Antioxidant Abilities of Enzymatic-Transesterification (-)-Epigallocatechin-3-O-gallate Stearyl Derivatives in Non-Aqueous Systems - Jiang_2021_Antioxidants.(Basel)_10_
Author(s) : Jiang C , Wang L , Huang X , Zhu S , Ma C , Wang H
Ref : Antioxidants (Basel) , 10 : , 2021
Abstract : Vinyl stearate was added to enzymatic transesterification of (-)-Epigallocatechin-3-O-gallate (EGCG) to enhance its lipophilicity and antioxidant ability in a non-aqueous system. The lipase DF "Amano" 15 was used as the catalyst. The optimal reaction conditions were: acetonitrile as the solvent, the molar ratio of vinyl stearate: EGCG as 3:1, an enzyme amount of 4.0% (ratio of substrate mass), and a reaction temperature and time of 50 degreesC and 96 h, respectively, achieving 65.2% EGCG conversion. HPLC-MS and NMR were used to determine the structure of EGCG stearyl derivative (3'',5''-2-O-stearyl-EGCG). The lipophilicity of EGCG stearyl derivatives (3.49 +/- 0.34) was higher (5.06 times) than that of the parent EGCG (0.69 +/- 0.08). Furthermore, EGCG stearyl derivatives had excellent lipid oxidation compared with BHT, BHA, and parent EGCG. The POVs of soybean oil with EGCG stearyl derivatives (18.17 +/- 0.92 mEq/kg) were significantly reduced (by 62.5%) at 21 d compared with those of EGCG (48.50 +/- 1.23 mEq/kg). These results indicate that EGCG derivatives have broad antioxidant application prospects in lipophilic environments/high-fat food.
ESTHER : Jiang_2021_Antioxidants.(Basel)_10_
PubMedSearch : Jiang_2021_Antioxidants.(Basel)_10_
PubMedID: 34439530

Title : Clinical Relevance and Prognostic Value of the Neuronal Protein Neuroligin 2 in Breast Cancer - Zhang_2021_Front.Oncol_11_630257
Author(s) : Zhang G , Sun Y , Wu ZS , Huang X
Ref : Front Oncol , 11 :630257 , 2021
Abstract : Neuroligin 2 (NLGN2) is a well-recognized transmembrane scaffolding protein that functions in synapse development and neuronal signal transduction. It has recently been implicated in multiple diseases of peripheral ectodermal origin. However, the potential roles of NLGN2 in tumors remain ill-defined. The aim of this study was to determine the clinical relevance and prognostic value of NLGN2 in breast cancer. To this end, breast cancer datasets were extracted from TCGA and other public databases, and subjected to Kaplan-Meier potter for survival analysis, GEPIA2 for assessing the immunological relevance of NLGN2 and THPA for identifying its subcellular localization. The in-silico results were further validated by immunohistochemistry analysis of in-house tumor tissue specimens. NLGN2 was identified as a prognostic factor in breast cancer subtypes, and its high expression correlated to a favorable survival outcome. Moreover, NLGN2 overexpression in breast cancer was significantly associated with large tumor size, lymph node metastasis, late TNM stage, and high histological grade. Interestingly, there was a significant correlation between the expression level of NLGN2 and the immunomodulatory molecules, along with increased interstitial infiltration of lymphocytes. Furthermore, NLGN2 was predominantly localized in the mitochondria of breast cancer cells. In conclusion, NLGN2 has a prognostic role and immunoregulatory potential in breast cancer, and its functions likely have a mitochondrial basis. It is a promising therapeutic target in breast cancer and should be explored further.
ESTHER : Zhang_2021_Front.Oncol_11_630257
PubMedSearch : Zhang_2021_Front.Oncol_11_630257
PubMedID: 34804909

Title : Structural characterization and antioxidant property of enzymatic-transesterification derivatives of (-)-epigallocatechin-3-O-gallate and vinyl laurate - Jiang_2021_J.Food.Sci__
Author(s) : Jiang C , Wang L , Huang X , Zhu S , Ma C , Wang H
Ref : J Food Sci , : , 2021
Abstract : (-)-Epigallocatechin-3-O-gallate(EGCG) was enzymatically modified to enhance the lipophilicity and the antioxidant property. The determination of optimal reaction conditions are as follows: Lipase DF "Amano" 15 and acetone were used as catalyst and solvent, respectively. Equal molar of EGCG and vinyl laurate (1:1); lipase addition of 6.0% (w/w of total substrates); reaction temperature of 50 degreesC and reaction time of 96 h, which obtained the conversion rate of EGCG at 80.1%. The structure of EGCG lauroyl derivatives were 5''-O-lauroyl-EGCG, 3'',5''-2-O-lauroyl-EGCG, and 5',3'',5''-3-O-lauroyl-EGCG, identified by high-performance liquid chromatography-mass spectrometry (HPLC-MS) and nuclear magnetic resonance (NMR). Compared with the logP of precursor EGCG (0.69 +/- 0.03), the logP of EGCG lauroyl derivatives was 1.37 +/- 0.19, 2.27 +/- 0.33, and 3.28 +/- 0.37, increasing by 0.98, 2.28, and 3.75 times, respectively (p < 0.05), suggesting the grafted fatty acid chains make EGCG derivatives more lipophilic, and the lipid solubility gradually increased as the number of substituents increased. Furthermore, EGCG lauroyl derivatives had excellent lipid oxidation than that of EGCG. The POVs (peroxide values) of soybean oil with mono-, di-, tri-lauroyl EGCG were significantly reduced by 42%, 47%, and 57% than that of EGCG at 21 days, respectively, indicating the antioxidative inhibition of these derivatives decreased with the increase in substituents. This indicates that these derivatives have broad prospects of the antioxidant application while improving their solubility properties in lipophilic environments/high-fat food. Practical Application: The lipophilic esterification reaction of EGCG catalyzed by new catalytic lipase DF "Amano" 15 was carried out in a non-aqueous solvent.Various reaction factors on a higher conversion rate of EGCG lauroyl derivatives were evaluated. The lipophilicity and antioxidant properties of EGCG lauroyl derivatives were much excellent than that of parent EGCG.
ESTHER : Jiang_2021_J.Food.Sci__
PubMedSearch : Jiang_2021_J.Food.Sci__
PubMedID: 34553787

Title : Growth Performance and Enzymatic Response of the Grasshopper, Calliptamus abbreviatus (Orthoptera: Acrididae), to Six Plant-Derived Compounds - Wang_2020_J.Insect.Sci_20_
Author(s) : Wang Y , Huang X , Chang BH , Zhang Z
Ref : J Insect Sci , 20 : , 2020
Abstract : Plant-derived compounds are sources of biopesticides for the control of insect pests. We compared the growth performance and enzymatic response of the grasshopper Calliptamus abbreviatus Ikonn to six plant-derived compounds (rutin, quercetin, nicotine, matrine, azadirachtin, and rotenone) in laboratory and field trials. When exposed to the six compounds, C. abbreviatus had significantly reduced growth and survival. All the compounds significantly induced an elevated level of reactive oxygen species, indicating oxidative damage. The activity of detoxifying enzymes, including cytochrome P450s, carboxylesterase, glutathione-S-transferase, and UDP-glucuronosyltransferase, and the antioxidant enzymes, including superoxide dismutase, catalase, and peroxidase, all significantly increased after exposure to the six compounds. These data suggest that the six plant-derived compounds had negative effects on C. abbreviatus. Of the six compounds, matrine, azadirachtin, and rotenone were more toxic to C. abbreviatus, followed by nicotine, quercetin, and rutin. These results show the potential of these compounds as botanical pesticides, which can be applied for the biological control of the grasshopper C. abbreviatus.
ESTHER : Wang_2020_J.Insect.Sci_20_
PubMedSearch : Wang_2020_J.Insect.Sci_20_
PubMedID: 32501501

Title : Discovery and Characterization of a PKS-NRPS Hybrid in Aspergillus terreus by Genome Mining - Tang_2020_J.Nat.Prod_83_473
Author(s) : Tang S , Zhang W , Li Z , Li H , Geng C , Huang X , Lu X
Ref : Journal of Natural Products , 83 :473 , 2020
Abstract : Fungal polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) hybrids have been characterized to produce polyketide-amino acid compounds with striking structural features and biological activities. In this study, a PKS-NRPS hybrid enzyme was found in Aspergillus terreus by genome mining. By activating the cluster-specific transcriptional regulator, this cryptic PKS-NRPS gene cluster was successfully activated and ten products (1-10) were identified as pyranterreones. Using functional genetics, bioinformatics, and isotope-labeling feeding analysis, the biosynthetic pathway was revealed. This is the second PKS-NRPS hybrid identified in A. terreus.
ESTHER : Tang_2020_J.Nat.Prod_83_473
PubMedSearch : Tang_2020_J.Nat.Prod_83_473
PubMedID: 32077283
Gene_locus related to this paper: asptn-pytb , aspte-pyti

Title : Identification, characterization and expression analyses of cholinesterases genes in Yesso scallop (Patinopecten yessoensis) reveal molecular function allocation in responses to ocean acidification - Xing_2020_Aquat.Toxicol_231_105736
Author(s) : Xing Q , Liao H , Peng C , Zheng G , Yang Z , Wang J , Lu W , Huang X , Bao Z
Ref : Aquat Toxicol , 231 :105736 , 2020
Abstract : Cholinesterases are key enzymes in central and peripheral cholinergic nerve system functioning on nerve impulse transmission in animals. Though cholinesterases have been identified in most vertebrates, the knowledge about the variable numbers and multiple functions of the genes is still quite meagre in invertebrates, especially in scallops. In this study, the complete cholinesterase (ChE) family members have been systematically characterized in Yesso scallop (Patinopecten yessoensis) via whole-genome scanning through in silico analysis. Ten ChE family members in the genome of Yesso scallop (designated PyChEs) were identified and potentially acted to be the largest number of ChE in the reported species to date. Phylogenetic and protein structural analyses were performed to determine the identities and evolutionary relationships of these genes. The expression profiles of PyChEs were determined in all developmental stages, in healthy adult tissues, and in mantles under low pH stress (pH 6.5 and 7.5). Spatiotemporal expression suggested the ubiquitous functional roles of PyChEs in all stages of development, as well as general and tissue-specific functions in scallop tissues. Regulation expressions revealed diverse up- and down-regulated expression patterns at most time points, suggesting different functional specialization of gene superfamily members in response to ocean acidification (OA). Evidences in gene number, phylogenetic relationships and expression patterns of PyChEs revealed that functional innovations and differentiations after gene duplication may result in altered functional constraints among PyChEs gene clusters. Collectively, our results provide the potential clues that the selection pressures coming from the environment were the potential inducement leading to function allocation of ChE family members in scallop.
ESTHER : Xing_2020_Aquat.Toxicol_231_105736
PubMedSearch : Xing_2020_Aquat.Toxicol_231_105736
PubMedID: 33422860
Gene_locus related to this paper: mizye-a0a210qls6 , mizye-a0a210qis3 , mizye-a0a210qg00 , mizye-a0a210r5n9 , mizye-a0a210qbv2 , mizye-a0a210pu25 , mizye-a0a210ptr6 , mizye-a0a210ptv1 , mizye-a0a210ptq0 , mizye-P021348901.2

Title : Collaborative Biosynthesis of a Class of Bioactive Azaphilones by Two Separate Gene Clusters Containing Four PKS\/NRPSs with Transcriptional Crosstalk in Fungi - Huang_2020_Angew.Chem.Int.Ed.Engl_59_4349
Author(s) : Huang X , Zhang W , Tang S , Wei S , Lu X
Ref : Angew Chem Int Ed Engl , 59 :4349 , 2020
Abstract : Azaphilones are a family of fungal polyketide metabolites with diverse chemical structures and biological activities with a highly oxygenated pyranoquinone bicyclic core. Here, a class of azaphilones possessing a 6/6/6/6 tetracyclic ring system was identified in Aspergillus terreus, and exhibited potential anticancer activities. The gene deletions and biochemical investigations demonstrated that these azaphilones were collaboratively synthesized by two separate clusters containing four core-enzymes, two nonreducing PKSs, one highly reducing PKS, and one NRPS-like. More interestingly, we found that the biosynthesis is coordinately regulated by a crosstalk mechanism between these two gene clusters based on three transcriptional factors. This is a meaningful mechanism of fungal secondary metabolism, which allows fungi to synthesize more complex compounds and gain new physiological functions. The results provide a new insight into fungal natural product biosynthesis.
ESTHER : Huang_2020_Angew.Chem.Int.Ed.Engl_59_4349
PubMedSearch : Huang_2020_Angew.Chem.Int.Ed.Engl_59_4349
PubMedID: 31908094
Gene_locus related to this paper: asptn-5moas , asptn-azpb5

Title : Induced fluorescent enhancement of protein-directed synthesized gold nanoclusters for selective and sensitive detection of flame retardants - Liu_2020_Sci.Total.Environ_713_136488
Author(s) : Liu H , Zhu N , Li M , Huang X , Wu P , Hu Z , Shuai J
Ref : Sci Total Environ , 713 :136488 , 2020
Abstract : Organophosphate flame retardants (OPFRs), typical toxic and hazardous pollutants, are called for new detection approaches to avoid laborious synthetic procedures and large and expensive instruments. Hence, a novel fluorescent probe was constructed for quantitative detection of OPFRs via heightening the fluorescence of acetylcholinesterase synthesized gold nanoclusters (AChE-AuNCs). The as-prepared AChE-AuNCs exhibited high fluorescence emission at about 398 nm with the average particle size of about 1.60 nm. When the AChE-AuNCs was applied to the proposed fluorescent detection, excellent sensitivity with wide linear range (50-1000 ng L(-1)) and low detection limit (30 ng L(-1)) for TClPP with the response time less than 1 h were achieved. The fluorescent probe could be extended to detect other three types of OPFRs (TEP, TPHP, and TBOEP) and the target pollutants could be detectable in the presence of halogenated flame retardants. The mechanism might be mainly contributed by the interaction between OPFRs and AChE-AuNCs restricting internal vibration consumption of their capping ligands. The proposed detection approach could be easily operated and was not involved with other intermediate products. Therefore, AChE-AuNCs could be a promising fluorescent probe for rapid, selective and sensitive detection of OPFRs and even in the practical application.
ESTHER : Liu_2020_Sci.Total.Environ_713_136488
PubMedSearch : Liu_2020_Sci.Total.Environ_713_136488
PubMedID: 31955081

Title : A novel esterase LanE from Edaphocola flava HME-24 and the enantioselective degradation mechanism of herbicide lactofen - Hu_2020_Ecotoxicol.Environ.Saf_205_111141
Author(s) : Hu T , Xiang Y , Chen Q , Shang N , Xu M , Huang X
Ref : Ecotoxicology & Environmental Safety , 205 :111141 , 2020
Abstract : Lactofen is a chiral herbicide and widely used against broadleaf weeds in agriculture. As a pesticide, it is directly released to the environment, and easily caused contamination in soil and aquatic ecosystem. The enantioselective degradation of lactofen in the environment has been reported, but the molecular biological mechanism of this phenomenon is still unclear. In this study, strain Edaphocola flava HME-24 could degrade 96.7% of 50 mg L(-1) lactofen within 72 h. Lactofen was initially hydrolyzed to desethyl lactofen and subsequently acifluorfen by strain HME-24. A novel gene lanE, involved in lactofen transformation, was obtained from Edaphocola flava HME-24. Gene lanE encoded a protein of 471 amino acids that contained the conserved GXSXG esterase motif and clustered into esterase subfamily V. LanE shared the highest identity with esterase EstD (Q9WYH1) from Thermotoga maritima MSB8 (29.14%). This esterase was also able to transform p-nitrophenyl esters (C4-C8), and the activity decreased when the carbon chain length increased. LanE showed enantioselectivity during the degradation of lactofen, diclofop-methyl, and quizalofop-ethyl, with a higher degradation efficiency of (S)-enantiomers than (R)-enantiomers. The three-dimensional structure of LanE was simulated, and molecular docking revealed that when the (S)-enantiomers of lactofen occupied the active sites, the distance between the ligand molecule and the coordination atom was shorter than that when the (R)-enantiomers occupied the active sites, which facilitated the formation of the transition state complex. The results in this study enhanced our understanding of the preferential catabolism of the (S)-enantiomers of lactofen on the molecular level and could illustrate the reported enantioselective degradation of lactofen in the environment.
ESTHER : Hu_2020_Ecotoxicol.Environ.Saf_205_111141
PubMedSearch : Hu_2020_Ecotoxicol.Environ.Saf_205_111141
PubMedID: 32846294
Gene_locus related to this paper: 9bact-a0a7g9u6e3

Title : Inhibitory mechanisms and interaction of tangeretin, 5-demethyltangeretin, nobiletin, and 5-demethylnobiletin from citrus peels on pancreatic lipase: Kinetics, spectroscopies, and molecular dynamics simulation - Huang_2020_Int.J.Biol.Macromol_164_1927
Author(s) : Huang X , Zhu J , Wang L , Jing H , Ma C , Kou X , Wang H
Ref : Int J Biol Macromol , 164 :1927 , 2020
Abstract : This study aimed to reveal the interaction and inhibitory mechanisms of tangeretin (TAN), nobiletin (NBT), and their acidic hydroxylated forms, 5-demethyltangeretin (5-DT) and 5-demethylnobiletin (5-DN) on porcine pancreatic lipase (PPL) using spectroscopic techniques and molecular dynamics (MD) simulation. PPL inhibition assay showed that the inhibitory activity of NBT (IC(50) value of 3.60 +/- 0.19 microM) was superior to those of three polymethoxylated flavones (PMFs), indicating it may be related to the methoxy groups at the 3'-position in its molecular structure. Inhibition kinetic analyses demonstrated that the inhibition types of the 4 PMFs were consistent with the mixed inhibition model, which agreed well with the results from the ultraviolet-visible (UV-Vis) spectroscopy, Circular dichroism (CD), fluorescence spectroscopy, molecular docking, and MD simulation that PMFs could bind to the PPL catalytic site and non-catalytic site, affecting the normal spatial conformation of PPL and weakening its ability to decompose the substrate. All these findings suggest that PMFs are a kind of natural lipase inhibitors, and NBT has the potential as a lipase inhibition precursor because of its unique flavone skeleton structure.
ESTHER : Huang_2020_Int.J.Biol.Macromol_164_1927
PubMedSearch : Huang_2020_Int.J.Biol.Macromol_164_1927
PubMedID: 32795575

Title : Alzheimer's Disease and Its Potential Alternative Therapeutics - Kisby_2019_J.Alzheimers.Dis.Parkinsonism_9_
Author(s) : Kisby B , Jarrell JT , Agar ME , Cohen DS , Rosin ER , Cahill CM , Rogers JT , Huang X
Ref : J Alzheimers Dis Parkinsonism , 9 : , 2019
Abstract : Alzheimer's Disease (AD) is a chronic neurodegenerative disease that affects over 5 million individuals in the United States alone. Currently, there are only two kinds of pharmacological interventions available for symptomatic relief of AD; Acetyl Cholinesterase Inhibitors (AChEI) and N-methyl-D-aspartic Acid (NMDA) receptor antagonists and these drugs do not slow down or stop the progression of the disease. Several molecular targets have been implicated in the pathophysiology of AD, such as the tau (tau) protein, Amyloid-beta (Abeta), the Amyloid Precursor Protein (APP) and more and several responses have also been observed in the advancement of the disease, such as reduced neurogenesis, neuroinflammation, oxidative stress and iron overload. In this review, we discuss general features of AD and several small molecules across different experimental AD drug classes that have been studied for their effects in the context of the molecular targets and responses associated with the AD progression. These drugs include: Paroxetine, Desferrioxamine (DFO), N-acetylcysteine (NAC), Posiphen/-(-)Phenserine, JTR-009, Carvedilol, LY450139, Intravenous immunoglobulin G 10%, Indomethacin and Lithium Carbonate (Li2CO3).
ESTHER : Kisby_2019_J.Alzheimers.Dis.Parkinsonism_9_
PubMedSearch : Kisby_2019_J.Alzheimers.Dis.Parkinsonism_9_
PubMedID: 31588368

Title : Large-scale separation of acetylcholinesterase inhibitors from Zanthoxylum nitidum by pH-zone-refining counter-current chromatography target-guided by ultrafiltration high-performance liquid chromatography with ultraviolet and mass spectrometry screening - Liu_2019_J.Sep.Sci_42_1194
Author(s) : Liu M , Liu Q , Chen M , Huang X , Chen X
Ref : J Sep Sci , 42 :1194 , 2019
Abstract : A new strategy by converging ultrafiltration high-performance liquid chromatography with ultraviolet and mass spectrometry and pH-zone-refining counter-current chromatography was developed for the rapid screening and separation of potential acetylcholinesterase inhibitors from the crude alkaloidals extract of Zanthoxylum nitidum. An optimized two-phase solvent system composed of chloroform/methanol/water (4:3:3, v/v) was used in this study. And, in the optimal solvent system, 45 mM hydrochloric acid was added to the aqueous stationary phase as the retainer, while 5 mM triethylamine was added to the organic mobile phase as the eluter. As a result, with the purity of over 95%, five alkaloids including jatrorrhizine (1, 340 mg), columbamine (2, 112 mg), skimmianine (3, 154 mg), palmatine (4, 226 mg), and epiberberine (5, 132 mg) were successfully purified in one step from 3.0 g crude alkaloidals extract. And their structures were identified by ultraviolet, mass spectrometry, (1) H and (13) C NMR spectroscopy. Notably, compounds 2, 4 and 5 were firstly reported in Z. nitidum. In addition, acetylcholinesterase inhibitory activities of compounds 1-5 were evaluated, and compounds 3, 4 and 5 exhibited stronger acetylcholinesterase inhibitory activity (IC50 values at 8.52 +/- 0.64, 14.82 +/- 1.21 and 3.12 +/- 0.32 mug/mL, respectively) than berberine (IC50 value at 32.86 +/- 2.14 mug/mL, positive control). The results indicated that the proposed method is an efficient technique to rapidly screen acetylcholinesterase inhibitors from complex samples, and could be served as a large-scale preparative technique for separating ionizable active compounds.
ESTHER : Liu_2019_J.Sep.Sci_42_1194
PubMedSearch : Liu_2019_J.Sep.Sci_42_1194
PubMedID: 30638299

Title : Selenepezil, a Selenium-Containing Compound, Exerts Neuroprotective Effect via Modulation of the Keap1-Nrf2-ARE Pathway and Attenuates Abeta-Induced Cognitive Impairment in Vivo - Yan_2019_ACS.Chem.Neurosci_10_2903
Author(s) : Yan J , Pang Y , Zhuang J , Lin H , Zhang Q , Han L , Ke P , Huang X
Ref : ACS Chem Neurosci , 10 :2903 , 2019
Abstract : Oxidative stress is a major risk factor for neurodegenerative disease. The Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2 related factor 2 (Nrf2)-antioxidant response element (ARE) pathway is one of the most potent defensive systems against oxidative stress. Selenepezil, a selenium-based compound, was previously found to exhibit excellent acetylcholinesterase (AChE) inhibition, to mimic endogenous glutathione peroxidase (GPx) activity, and to exhibit scavenging activity for hydrogen peroxide in vitro. However, none of these activities have been evaluated in a cellular model, and detailed molecular mechanisms are not elucidated. Moreover, whether selenepezil ameliorates memory deficits in vivo remains unknown. This study validated the cytoprotective effect of selenepezil against 6-hydroxydopamine (6-OHDA)- or H2O2-induced SH-SY5Y cell damage via alleviation or neutralization of intracellular microtubule disorder, reactive oxygen species (ROS) accumulation, mitochondrial dysfunction, and cell apoptosis. Our study clearly demonstrated that selenepezil pretreatment exhibited remarkable cytoprotective effect in a Nrf2-dependent manner via activating the Keap1-Nrf2-ARE pathway and stimulating the transcription of Nrf2-ARE-regulated cytoprotective genes. Moreover, selenepezil.HCl exerts neuroprotective effect via attenuating Abeta-induced cognitive impairment in Alzheimer's disease (AD) rat and was more active than the reference drug donepezil. In summary, selenepezil deserves further consideration for AD therapy.
ESTHER : Yan_2019_ACS.Chem.Neurosci_10_2903
PubMedSearch : Yan_2019_ACS.Chem.Neurosci_10_2903
PubMedID: 31035749

Title : Detoxification of diphenyl ether herbicide lactofen by Bacillus sp. Za and enantioselective characteristics of an esterase gene lacE - Zhang_2018_J.Hazard.Mater_341_336
Author(s) : Zhang J , Lu L , Chen F , Chen L , Yin J , Huang X
Ref : J Hazard Mater , 341 :336 , 2018
Abstract : A bacterial strain Za capable of degrading diphenyl ether herbicide lactofen was isolated and identified as Bacillus sp. This strain could degrade 94.8% of 50mgL-1 lactofen after 4days of inoculation in flasks. It was revealed that lactofen was initially hydrolyzed to desethyl lactofen, which was further transformed to acifluorfen, followed by the reduction of the nitro group to yield aminoacifluorfen. The phytotoxicity of the transformed product aminoacifluorfen to maize was decreased significantly compared with the lactofen. A gene lacE, encoding an esterase responsible for lactofen hydrolysis to desethyl lactofen and acifluorfen continuously, was cloned from Bacillus sp. Za. The deduced amino acid belonging to the esterase family VII contained a typical Ser-His-Asp/Glu catalytic triad and the conserved motifs GXSXG. The purified recombinant protein LacE displayed maximal esterase activity at 40 degrees C and pH 7.0. Additionally, LacE had broad substrate specificity and was capable of hydrolyzing p-nitrophenyl esters. The enantioselectivity of LacE during lactofen degradation was further studied, and the results indicated that the (S)-(+)-lactofen was degraded faster than the (R)-(-)-lactofen, which could illustrate the reported phenomenon that (S)-(+)-lactofen was preferentially degraded in soil and sediment.
ESTHER : Zhang_2018_J.Hazard.Mater_341_336
PubMedSearch : Zhang_2018_J.Hazard.Mater_341_336
PubMedID: 28802244
Gene_locus related to this paper: bacsu-pnbae

Title : Tat-Independent Secretion of Polyethylene Terephthalate Hydrolase PETase in Bacillus subtilis 168 Mediated by Its Native Signal Peptide - Huang_2018_J.Agric.Food.Chem_66_13217
Author(s) : Huang X , Cao L , Qin Z , Li S , Kong W , Liu Y
Ref : Journal of Agricultural and Food Chemistry , 66 :13217 , 2018
Abstract : Widespread utilization of polyethylene terephthalate (PET) has caused critical environmental pollution. The enzymatic degradation of PET is a promising solution to this problem. In this study, PETase, which exhibits much higher PET-hydrolytic activity than other enzymes, was successfully secreted into extracellular milieu from Bacillus subtilis 168 under the direction of its native signal peptide (named SP(PETase)). SP(PETase) is predicted to be a twin-arginine signal peptide. Intriguingly, inactivation of twin-arginine translocation (Tat) complexes improved the secretion amount by 3.8-fold, indicating that PETase was exported via Tat-independent pathway. To the best of our knowledge, this is the first report on the improvement of Tat-independent secretion by inactivating Tat components of B. subtilis 168 in LB medium. Furthermore, PET film degradation assay showed that the secreted PETase was fully active. This study paves the first step to construct an efficient engineered strain for PET degradation.
ESTHER : Huang_2018_J.Agric.Food.Chem_66_13217
PubMedSearch : Huang_2018_J.Agric.Food.Chem_66_13217
PubMedID: 30465427

Title : Effects of soil acidification on the toxicity of organophosphorus pesticide on Eisenia fetida and its mechanism - Zou_2018_J.Hazard.Mater_359_365
Author(s) : Zou X , Xiao X , Zhou H , Chen F , Zeng J , Wang W , Feng G , Huang X
Ref : J Hazard Mater , 359 :365 , 2018
Abstract : Organophosphorus pesticides (OPs) have been widely used to control agricultural insects. Soil acidification is a major problem in soil of intensive agricultural systems, especially in red soil with a low pH buffer capacity. However, the effects of soil acidification on the toxicity of pesticides are still unclear. In the present study, the toxicity of three OPs on E. fetida was determined at individual (14-day lethal test) and biochemical levels (antioxidative defence enzymes) by using acidified soils (pH=5.5, 4.3 and 3.1). The results showed that the toxicity of tested OPs was slightly increased with the decrease of soil pH. To interpret the phenomena, an optimum Quantitative Structure Activity Relationship (QSAR) model was developed based on the toxicity mechanism and the partial least squares regression (PLS) method. The model indicated bioavailability and toxicodynamics are key factors of soil acidification affecting the toxicity of the OPs. Further results revealed the bioavailability of the OPs was strongly related to their hydrolysis and biodegradation character, whereas the effects of soil acidification on toxicodynamics were mainly caused by the interaction between the acetylcholinesterase (AchE) and the OPs. Results will increase understanding of the effects of soil acidification on the toxicity of pesticides and its mechanism.
ESTHER : Zou_2018_J.Hazard.Mater_359_365
PubMedSearch : Zou_2018_J.Hazard.Mater_359_365
PubMedID: 30048951

Title : Biology, physiology and gene expression of grasshopper Oedaleus asiaticus exposed to diet stress from plant secondary compounds - Huang_2017_Sci.Rep_7_8655
Author(s) : Huang X , Ma J , Qin X , Tu X , Cao G , Wang G , Nong X , Zhang Z
Ref : Sci Rep , 7 :8655 , 2017
Abstract : We studied the role of plant primary and secondary metabolites in mediating plant-insect interactions by conducting a no-choice single-plant species field experiment to compare the suitability, enzyme activities, and gene expression of Oedaleus asiaticus grasshoppers feeding on four host and non-host plants with different chemical traits. O. asiaticus growth showed a positive relationship to food nutrition content and a negative relationship to secondary compounds content. Grasshopper amylase, chymotrypsin, and lipase activities were positively related to food starch, crude protein, and lipid content, respectively. Activity of cytochrome P450s, glutathione-S-transferase, and carboxylesterase were positively related to levels of secondary plant compounds. Gene expression of UDP-glucuronosyltransferase 2C1, cytochrome P450 6K1 were also positively related to secondary compounds content in the diet. Grasshoppers feeding on Artemisia frigida, a species with low nutrient content and a high level of secondary compounds, had reduced growth and digestive enzyme activity. They also had higher detoxification enzyme activity and gene expression compared to grasshoppers feeding on the grasses Cleistogenes squarrosa, Leymus chinensis, or Stipa krylovii. These results illustrated Oedaleus asiaticus adaptive responses to diet stress resulting from toxic chemicals, and support the hypothesis that nutritious food benefits insect growth, but plant secondary compounds are detrimental for insect growth.
ESTHER : Huang_2017_Sci.Rep_7_8655
PubMedSearch : Huang_2017_Sci.Rep_7_8655
PubMedID: 28819233

Title : Scallop genome provides insights into evolution of bilaterian karyotype and development - Wang_2017_Nat.Ecol.Evol_1_120
Author(s) : Wang S , Zhang J , Jiao W , Li J , Xun X , Sun Y , Guo X , Huan P , Dong B , Zhang L , Hu X , Sun X , Wang J , Zhao C , Wang Y , Wang D , Huang X , Wang R , Lv J , Li Y , Zhang Z , Liu B , Lu W , Hui Y , Liang J , Zhou Z , Hou R , Li X , Liu Y , Li H , Ning X , Lin Y , Zhao L , Xing Q , Dou J , Mao J , Guo H , Dou H , Li T , Mu C , Jiang W , Fu Q , Fu X , Miao Y , Liu J , Yu Q , Li R , Liao H , Kong Y , Jiang Z , Chourrout D , Bao Z
Ref : Nat Ecol Evol , 1 :120 , 2017
Abstract : Reconstructing the genomes of bilaterian ancestors is central to our understanding of animal evolution, where knowledge from ancient and/or slow-evolving bilaterian lineages is critical. Here we report a high-quality, chromosome-anchored reference genome for the scallop Patinopecten yessoensis, a bivalve mollusc that has a slow-evolving genome with many ancestral features. Chromosome-based macrosynteny analysis reveals a striking correspondence between the 19 scallop chromosomes and the 17 presumed ancestral bilaterian linkage groups at a level of conservation previously unseen, suggesting that the scallop may have a karyotype close to that of the bilaterian ancestor. Scallop Hox gene expression follows a new mode of subcluster temporal co-linearity that is possibly ancestral and may provide great potential in supporting diverse bilaterian body plans. Transcriptome analysis of scallop mantle eyes finds unexpected diversity in phototransduction cascades and a potentially ancient Pax2/5/8-dependent pathway for noncephalic eyes. The outstanding preservation of ancestral karyotype and developmental control makes the scallop genome a valuable resource for understanding early bilaterian evolution and biology.
ESTHER : Wang_2017_Nat.Ecol.Evol_1_120
PubMedSearch : Wang_2017_Nat.Ecol.Evol_1_120
PubMedID: 28812685
Gene_locus related to this paper: mizye-a0a210qls6 , mizye-a0a210qis3 , mizye-a0a210qg00 , mizye-a0a210ped6 , mizye-a0a210q4h5 , mizye-a0a210q4h9 , mizye-a0a210q4j1 , mizye-a0a210qf86 , mizye-a0a210q332 , mizye-a0a210pqn0 , mizye-a0a210q7t5 , mizye-a0a210pij5 , mizye-a0a210qyk8 , mizye-a0a210pwl7 , mizye-a0a210q8u5 , mizye-a0a210r5n9 , mizye-a0a210qbv2 , mizye-a0a210pu25 , mizye-a0a210pek1 , mizye-a0a210pul3 , mizye-a0a210pum3 , mizye-a0a210ptr6 , mizye-a0a210ptq5 , mizye-a0a210ptc4.1 , mizye-a0a210ptc4.2 , mizye-a0a210ptv1 , mizye-a0a210ptv7 , mizye-a0a210qgl6 , mizye-a0a210qg90 , mizye-a0a210ptq0 , mizye-a0a210qg72 , mizye-a0a210ptb1 , mizye-a0a210pjd3 , mizye-a0a210qg92 , mizye-a0a210q8v2 , mizye-a0a210qg93 , mizye-a0a210q160.1 , mizye-a0a210q160.2 , mizye-a0a210qes4 , mizye-a0a210pk25 , mizye-a0a210q1b8 , mizye-a0a210q110 , mizye-a0a210r503 , mizye-P021348901.1 , mizye-P021348901.2

Title : Acetylcholinesterase Inhibitory Meroterpenoid from a Mangrove Endophytic Fungus Aspergillus sp. 16-5c - Long_2017_Molecules_22_
Author(s) : Long Y , Cui H , Liu X , Xiao Z , Wen S , She Z , Huang X
Ref : Molecules , 22 : , 2017
Abstract : One new meroterpenoid, named 2-hydroacetoxydehydroaustin (1), together with nine known meroterpenoids, 11-acetoxyisoaustinone (2), isoaustinol (3), austin (4), austinol (5), acetoxydehydroaustin (6), dehydroaustin (7), dehydroaustinol (8), preaustinoid A2 (9), and 1,2-dihydro-acetoxydehydroaustin B (10), were isolated from the mangrove endophytic fungus, Aspergillus sp. 16-5c. These structures were characterized by spectroscopic analysis, further the absolute configurations of stereogenic carbons for Compounds 1, 3, 4, 6, 7, 8, 9, and 10 were determined by single crystal X-ray diffraction analysis using Cu Kalpha radiation. Moreover, the absolute configurations of stereogenic carbons for Known Compounds 3, 7, 8, and 9 are identified here for the first time. Compounds 3, 7, and 8 showed acetylcholinesterase (AchE) inhibitory activity with IC50 values of 2.50, 0.40, and 3.00 muM, respectively.
ESTHER : Long_2017_Molecules_22_
PubMedSearch : Long_2017_Molecules_22_
PubMedID: 28467349

Title : Interaction of a digestive protease, Candida rugosa lipase, with three surfactants investigated by spectroscopy, molecular docking and enzyme activity assay - Zhang_2017_Sci.Total.Environ_622-623_306
Author(s) : Zhang R , Liu Y , Huang X , Xu M , Liu R , Zong W
Ref : Sci Total Environ , 622-623 :306 , 2017
Abstract : The extensive use of surfactants in food, laundry products and agriculture has caused concern about their biosafety. However, few studies have been done on their potential effect on the lipase which has always been used with surfactants in food and laundry industry. Herein, we investigated the interaction of three surfactants (sodium dodecyl sulfate (SDS), sodium dodecyl benzene sulfonate (SDBS), sodium lauryl sulfonate (SLS)) with Candida rugosa lipase (CRL), which is a popular biocatalyst used regularly with surfactants. The effect of the three surfactants on the conformation and activity of CRL was evaluated by using multiple spectral methods, enzyme activity assay and molecular docking modeling. The results demonstrated that CRL interacted with SDS, SDBS and SLS primarily through hydrophobic forces, H-bonding and electrostatic forces, respectively. The binding constants (KA) of SDBS with CRL varied with temperature: 1.99x10(3)mol/L at 298K and 4.13x10(3)mol/L at 318K. SDS and SDBS affected the secondary structure and skeleton of CRL, which changed the polarity of CRL and enhanced its activity. SLS also changed the secondary structure and activity of CRL moderately, but had little effect on its polarity and chromophore microenvironment. Accordingly, all three surfactants exhibited effect to CRL on the molecular level calling for more attention to pay on their biosafety. The work demonstrates that SDS, SDBS and SLS could cause negative effects to CRL from different angles and therefore are not bio-friendly detergents.
ESTHER : Zhang_2017_Sci.Total.Environ_622-623_306
PubMedSearch : Zhang_2017_Sci.Total.Environ_622-623_306
PubMedID: 29220758

Title : Carboxylesterase-involved metabolism of di-n-butyl phthalate in pumpkin (Cucurbita moschata) seedlings - Lin_2017_Environ.Pollut_220_421
Author(s) : Lin Q , Chen S , Chao Y , Huang X , Wang S , Qiu R
Ref : Environ Pollut , 220 :421 , 2017
Abstract : Uptake and accumulation by plants is a significant pathway in the migration and transformation of phthalate esters (PAEs) in the environment. However, limited information is available on the mechanisms of PAE metabolism in plants. Here, we investigated the metabolism of di-n-butyl phthalate (DnBP), one of the most frequently detected PAEs, in pumpkin (Cucurbita moschata) seedlings via a series of hydroponic experiments with an initial concentration of 10 mg L(-1). DnBP hydrolysis occurred primarily in the root, and two of its metabolites, mono-n-butyl phthalate (MnBP) and phthalic acid (PA), were detected in all plant tissues. The MnBP concentration was an order of magnitude higher than that of PA in shoots, which indicated MnBP was more readily transported to the shoot than was PA because of the former's dual hydrophilic and lipophilic characteristics. More than 80% of MnBP and PA were located in the cell water-soluble component except that 96% of MnBP was distributed into the two solid cellular fractions (i.e., cell wall and organelles) at 96 h. A 13-20% and 29-54% increase of carboxylesterase (CXE) activity shown in time-dependent and concentration-dependent experiments, respectively, indicated the involvement of CXEs in plant metabolism of DnBP. The level of CXE activity in root subcellular fractions was in the order: the cell water-soluble component (88-94%) >> cell wall (3-7%) > cell organelles (3-4%), suggesting that the cell water-soluble component is the dominant locus of CXE activity and also the domain of CXE-catalyzed hydrolysis of DnBP. The addition of triphenyl phosphate, a CXE inhibitor, led to 43-56% inhibition of CXE activity and 16-25% increase of DnBP content, which demonstrated the involvement of CXEs in plant metabolism of DnBP. This study contributes to our understanding of enzymitic mechanisms of PAE transformation in plants.
ESTHER : Lin_2017_Environ.Pollut_220_421
PubMedSearch : Lin_2017_Environ.Pollut_220_421
PubMedID: 27697378

Title : Biochemical characterization of an enantioselective esterase from Brevundimonas sp. LY-2 - Zhang_2017_Microb.Cell.Fact_16_112
Author(s) : Zhang J , Zhao M , Yu D , Yin J , Zhang H , Huang X
Ref : Microb Cell Fact , 16 :112 , 2017
Abstract : BACKGROUND: Lactofen, a member of the diphenylether herbicides, has high activity and is commonly used to control broadleaf weeds. As a post-emergent herbicide, it is directly released to the environment, and easily caused the pollution. This herbicide is degraded in soil mainly by microbial activity, but the functional enzyme involved in the biodegradation of lactofen is still not clear now.
RESULTS: A novel esterase gene lacH, involved in the degradation of lactofen, was cloned from the strain Brevundimonas sp. LY-2. The gene contained an open reading frame of 921 bp, and a putative signal peptide at the N-terminal was identified with the most likely cleavage site between Ala 28 and Ala 29. The encoded protein, LacH, could catalyze the hydrolysis of lactofen to form acifluorfen. Phylogenetic analysis showed that LacH belong to family V of bacterial lipolytic enzymes. Biochemical characterization analysis showed that LacH was a neutral esterase with an optimal pH of 7.0 and an optimal temperature of 40 degrees C toward lactofen. Besides, the activity of LacH was strongly inhibited by Hg2+ and Zn2+. LacH preferred short chain p-nitrophenyl esters (C2-C6), exhibited maximum activity toward p-nitrophenyl acetate. Furthermore, the enantioselectivity of LacH during lactofen hydrolysis was also studied, and the results show that R-(-)-lactofen was degraded faster than S-(+)-lactofen, indicating the occurrence of enantioselectivity in the enzymatic reaction.
CONCLUSIONS: Our studies characterized a novel esterase involved in the biodegradation of diphenylether herbicide lactofen. The esterase showed enantioselectivity during lactofen degradation, which revealed the occurrence of enzyme-mediated enantioselective degradation of chiral herbicides.
ESTHER : Zhang_2017_Microb.Cell.Fact_16_112
PubMedSearch : Zhang_2017_Microb.Cell.Fact_16_112
PubMedID: 28629408
Gene_locus related to this paper: 9caul-s5rrx5

Title : Computational design of cephradine synthase in a new scaffold identified from structural databases - Huang_2017_Chem.Commun.(Camb)_53_7604
Author(s) : Huang X , Xue J , Zhu Y
Ref : Chem Commun (Camb) , 53 :7604 , 2017
Abstract : Computational enzyme design exhibits excellent performance for identifying potential scaffolds from structural databases and creating new enzymatic catalysts from naught. Using the active site-matching algorithm ProdaMatch, we identified a new scaffold cocaine esterase from Rhodococcus sp. that showed modest activity (kcat/Km = 0.018 M-1 s-1) towards the hydrolysis of beta-lactam antibiotic cephradine. The identified cocaine esterase scaffold afforded low sequence identity (<30%) with the known beta-lactam synthases, such as penicillin G acylase or alpha-amino acid ester hydrolase, and was able to catalyze the condensation reaction between d-dihydrophenylglycine methyl ester and 7-aminodesacetoxycephalosporanic acid to produce cephradine via a kinetically controlled synthesis. By virtue of the computational enzyme design protocol, hundreds of sequences were predicted in the cocaine esterase scaffold to promote the catalytic activity towards the hydrolytic reaction of cephradine. Moreover, a single mutant (F261T) was experimentally confirmed to have improved the catalytic efficiency by ten times (kcat/Km = 0.193 M-1 s-1), indicating that the novel scaffold cocaine esterase may be potentially redesigned to become an industrially useful cephradine synthase.
ESTHER : Huang_2017_Chem.Commun.(Camb)_53_7604
PubMedSearch : Huang_2017_Chem.Commun.(Camb)_53_7604
PubMedID: 28639649
Gene_locus related to this paper: rhosm-cocE

Title : Bioactive alpha-pyrone meroterpenoids from mangrove endophytic fungus Penicillium sp - Ding_2016_Nat.Prod.Res__1
Author(s) : Ding B , Wang Z , Huang X , Liu Y , Chen W , She Z
Ref : Nat Prod Res , :1 , 2016
Abstract : Five alpha-pyrone meroterpenoids, including one new 3-epiarigsugacin E (1) and four known compounds, arisugacin D (2), arisugacin B (3), territrem C (4) and terreulactone C (5) were obtained from the marine fungus Penicillium sp. SK5GW1L. Their structures were identified by MS and NMR experiments, and the absolute configuration of compound 1 was further confirmed by low temperature (150 K) single crystal X-ray diffraction with Cu Kalpha radiation. Compounds 3, 4 and 5 showed strong inhibitory activities against acetylcholinesterase (AchE) with IC50 values of 3.03, 0.23 and 0.028 muM, respectively.
ESTHER : Ding_2016_Nat.Prod.Res__1
PubMedSearch : Ding_2016_Nat.Prod.Res__1
PubMedID: 27067533

Title : Identification of biotransformation enzymes in the antennae of codling moth Cydia pomonella - Huang_2016_Gene_580_73
Author(s) : Huang X , Liu L , Su X , Feng J
Ref : Gene , 580 :73 , 2016
Abstract : Biotransformation enzymes are found in insect antennae and play a critical role in degrading xenobiotics and odorants. In Cydia pomonella, we identified 26 biotransformation enzymes. Among these enzymes, twelve carboxylesterases (CXEs), two aldehyde oxidases (AOXs) and six alcohol dehydrogenases (ADs) were predominantly expressed in antennae. Each of the CpomCXEs presents a conserved catalytic triad "Ser-His-Glu", which is the structural characteristic of known insect CXEs. CpomAOXs present two redox centers, a FAD-binding domain and a molybdenum cofactor/substrate-binding domain. The antennal CpomADs are from two protein families, short-chain dehydrogenases/reducetases (SDRs) and medium-chain dehydrogenases/reducetases (MDRs). Putative catalytic active domain and cofactor binding domain were found in these CpomADs. Potential functions of these enzymes were determined by phylogenetic analysis. The results showed that these enzymes share close relationship with odorant degrading enzymes (ODEs) and resistance-associated enzymes of other insect species. Because of commonly observed roles of insect antennal biotransformation enzymes, we suggest antennal biotransformation enzymes presented here are candidate that involved in degradation of odorants and xenobiotics within antennae of C. pomonella.
ESTHER : Huang_2016_Gene_580_73
PubMedSearch : Huang_2016_Gene_580_73
PubMedID: 26778204

Title : Soluble epoxide hydrolase inhibition provides multi-target therapeutic effects in rats after spinal cord injury - Chen_2016_Mol.Neurobiol_53_1565
Author(s) : Chen X , Huang X , Qin C , Fang Y , Liu Y , Zhang G , Pan D , Wang W , Xie M
Ref : Molecular Neurobiology , 53 :1565 , 2016
Abstract : Multiple players are involved in motor and sensory dysfunctions after spinal cord injury (SCI). Therefore, therapeutic approaches targeting these various players in the damage cascade hold considerable promise for the treatment of traumatic spinal cord injury. Soluble epoxide hydrolase (sEH) is an endogenous key enzyme in the metabolic conversion and degradation of P450 eicosanoids called epoxyeicosatrienoic acids (EETs). sEH inhibition has been shown to provide neuroprotective effects upon multiple elements of neurovascular unit under cerebral ischemia. However, its role in the pathological process after SCI remains unclear. In this study, we tested the hypothesis that sEH inhibition may have therapeutic effects in preventing secondary damage in rats after traumatic SCI. sEH was widely expressed in spinal cord tissue, mainly confined to astrocytes, and neurons. Administration of sEH inhibitor AUDA significantly suppressed local inflammatory responses as indicated by the reduced microglia activation and IL-1 beta expression, as well as the decreased infiltration of neutrophils and T lymphocytes. Meanwhile, reactive astrogliosis was remarkably attenuated. Furthermore, treatment of AUDA improved angiogenesis, inhibited neuron cells apoptosis, alleviated demyelination and formation of cavity and improved motor recovery. Together, these results provide the first in vivo evidence that sEH inhibition could exert multiple targets protective effects after SCI in rats. sEH may thereby serve as a promising multi-mechanism therapeutic target for the treatment of SCI.
ESTHER : Chen_2016_Mol.Neurobiol_53_1565
PubMedSearch : Chen_2016_Mol.Neurobiol_53_1565
PubMedID: 25663200

Title : Free energy profiles of cocaine esterase-cocaine binding process by molecular dynamics and potential of mean force simulations - Zhang_2016_Chem.Biol.Interact_259_142
Author(s) : Zhang Y , Huang X , Han K , Zheng F , Zhan CG
Ref : Chemico-Biological Interactions , 259 :142 , 2016
Abstract : The combined molecular dynamics (MD) and potential of mean force (PMF) simulations have been performed to determine the free energy profile of the CocE)-(+)-cocaine binding process in comparison with that of the corresponding CocE-(-)-cocaine binding process. According to the MD simulations, the equilibrium CocE-(+)-cocaine binding mode is similar to the CocE-(-)-cocaine binding mode. However, based on the simulated free energy profiles, a significant free energy barrier ( approximately 5 kcal/mol) exists in the CocE-(+)-cocaine binding process whereas no obvious free energy barrier exists in the CocE-(-)-cocaine binding process, although the free energy barrier of approximately 5 kcal/mol is not high enough to really slow down the CocE-(+)-cocaine binding process. In addition, the obtained free energy profiles also demonstrate that (+)-cocaine and (-)-cocaine have very close binding free energies with CocE, with a negligible difference ( approximately 0.2 kcal/mol), which is qualitatively consistent with the nearly same experimental KM values of the CocE enzyme for (+)-cocaine and (-)-cocaine. The consistency between the computational results and available experimental data suggests that the mechanistic insights obtained from this study are reasonable.
ESTHER : Zhang_2016_Chem.Biol.Interact_259_142
PubMedSearch : Zhang_2016_Chem.Biol.Interact_259_142
PubMedID: 27163853

Title : Suppressive subtractive hybridization reveals different gene expression between high and low virulence strains of Cladosporium cladosporioides - Gu_2016_Microb.Pathog_100_276
Author(s) : Gu Y , Liu Y , Cao S , Huang X , Zuo Z , Yu S , Deng J , Ding C , Yuan M , Shen L , Wu R , Wen Y , Ren Z , Zhao Q , Peng G , Zhong Z , Wang C , Ma X
Ref : Microb Pathog , 100 :276 , 2016
Abstract : Cladosporium cladosporioides is a ubiquitous fungus, causing infections in plants, humans, and animals. Suppression subtractive hybridization (SSH) and quantitative real-time PCR (qRT-PCR) were used in this study to identify differences in gene expression between two C. cladosporioides strains, the highly virulent Z20 strain and the lowly virulent Zt strain. A total of 61 unigenes from the forward library and 42 from the reverse library were identified. Gene ontology (GO) analysis showed that these genes were involved in various biological processes, cellular components and molecular functions. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the unigenes in the forward library corresponded to 5 different pathways and the reverse library unigenes were involved in 3 different pathways. The qRT-PCR results indicated that expressions of APL1, GUD1, CSE1, SPBC3E7.04c and MFS were significantly different between Z20 and Zt strains, while genes encoding the senescence-associated proteins, pse1, nup107, mip1, pex2, icl1 and alpha/beta hydrolase exhibited no significant differences between the two strains. In addition, we found that 5 unigenes encoding mip1, chk1, icl1, alpha/beta hydrolase and beta-glucosidase may be associated with pathogenicity. One unigene (MFS) may be related to the resistance to 14 alpha-demethylase inhibitor fungicides, and 5 unigenes (PEX2, NUP107, PSE1, APL1, and SPBC3E7.04c) may be related to either low spore yield or earlier aging of the Zt strain. Our study may help better understand the molecular mechanism of C. cladosporioides infection, and therefore improve the treatment and prevention of C. cladosporioides induced diseases.
ESTHER : Gu_2016_Microb.Pathog_100_276
PubMedSearch : Gu_2016_Microb.Pathog_100_276
PubMedID: 27744104

Title : Identification and Characterization of ML352: A Novel, Noncompetitive Inhibitor of the Presynaptic Choline Transporter - Ennis_2015_ACS.Chem.Neurosci_6_417
Author(s) : Ennis EA , Wright J , Retzlaff CL , McManus OB , Lin Z , Huang X , Wu M , Li M , Daniels JS , Lindsley CW , Hopkins CR , Blakely RD
Ref : ACS Chem Neurosci , 6 :417 , 2015
Abstract : The high-affinity choline transporter (CHT) is the rate-limiting determinant of acetylcholine (ACh) synthesis, yet the transporter remains a largely undeveloped target for the detection and manipulation of synaptic cholinergic signaling. To expand CHT pharmacology, we pursued a high-throughput screen for novel CHT-targeted small molecules based on the electrogenic properties of transporter-mediated choline transport. In this effort, we identified five novel, structural classes of CHT-specific inhibitors. Chemical diversification and functional analysis of one of these classes identified ML352 as a high-affinity (Ki = 92 nM) and selective CHT inhibitor. At concentrations that fully antagonized CHT in transfected cells and nerve terminal preparations, ML352 exhibited no inhibition of acetylcholinesterase (AChE) or cholineacetyltransferase (ChAT) and also lacked activity at dopamine, serotonin, and norepinephrine transporters, as well as many receptors and ion channels. ML352 exhibited noncompetitive choline uptake inhibition in intact cells and synaptosomes and reduced the apparent density of hemicholinium-3 (HC-3) binding sites in membrane assays, suggesting allosteric transporter interactions. Pharmacokinetic studies revealed limited in vitro metabolism and significant CNS penetration, with features predicting rapid clearance. ML352 represents a novel, potent, and specific tool for the manipulation of CHT, providing a possible platform for the development of cholinergic imaging and therapeutic agents.
ESTHER : Ennis_2015_ACS.Chem.Neurosci_6_417
PubMedSearch : Ennis_2015_ACS.Chem.Neurosci_6_417
PubMedID: 25560927

Title : Developmental expression of the N-myc downstream regulated gene (Ndrg) family during Xenopus tropicalis embryogenesis - Zhong_2015_Int.J.Dev.Biol_59_511
Author(s) : Zhong C , Zhou YK , Yang SS , Zhao JF , Zhu XL , Chen HH , Chen PC , Huang LQ , Huang X
Ref : Int J Developmental Biology , 59 :511 , 2015
Abstract : The N-myc downstream regulated gene (Ndrg) family consists of four main members Ndrg1, 2, 3, and 4. The Ndrg genes are involved in many vital biological events including development. However, comprehensive expression patterns of this gene family during vertebrate embryogenesis remain largely unknown. Here, we analyzed the Ndrg family from the evolutionary perspective and examined the expression patterns of the Ndrg genes during Xenopus tropicalis embryogenesis. Different Ndrg family members of vertebrates are separated into different homology clusters which can be further classified into two groups and each Ndrg family member is well conserved during evolution. The temporal and spatial expression patterns of Ndrg1, 2, 3 and 4 are different during early Xenopus tropicalis development. Ndrg1, 2 and 4 are maternally expressed genes while Ndrg3 is a zygotically expressed gene. The Ndrg genes are differentially expressed in the developing central nervous system, the developing sensory organs, and the developing excretory organs. Moreover, they also show other specific expression domains. Our results indicate that the Ndrg genes exhibit specific expression patterns and may play different roles during vertebrate embryogenesis.
ESTHER : Zhong_2015_Int.J.Dev.Biol_59_511
PubMedSearch : Zhong_2015_Int.J.Dev.Biol_59_511
PubMedID: 26864492

Title : Kinetic characterization of a cocaine hydrolase engineered from mouse butyrylcholinesterase - Chen_2015_Biochem.J_466_243
Author(s) : Chen X , Huang X , Geng L , Xue L , Hou S , Zheng X , Brimijoin S , Zheng F , Zhan CG
Ref : Biochemical Journal , 466 :243 , 2015
Abstract : Mouse butyrylcholinesterase (mBChE) and an mBChE-based cocaine hydrolase (mCocH, i.e. the A199S/S227A/S287G/A328W/Y332G mutant) have been characterized for their catalytic activities against cocaine, i.e. naturally occurring (-)-cocaine, in comparison with the corresponding human BChE (hBChE) and an hBChE-based cocaine hydrolase (hCocH, i.e. the A199S/F227A/S287G/A328W/Y332G mutant). It has been demonstrated that mCocH and hCocH have improved the catalytic efficiency of mBChE and hBChE against (-)-cocaine by ~8- and ~2000-fold respectively, although the catalytic efficiencies of mCocH and hCocH against other substrates, including acetylcholine (ACh) and butyrylthiocholine (BTC), are close to those of the corresponding wild-type enzymes mBChE and hBChE. According to the kinetic data, the catalytic efficiency (kcat/KM) of mBChE against (-)-cocaine is comparable with that of hBChE, but the catalytic efficiency of mCocH against (-)-cocaine is remarkably lower than that of hCocH by ~250-fold. The remarkable difference in the catalytic activity between mCocH and hCocH is consistent with the difference between the enzyme-(-)-cocaine binding modes obtained from molecular modelling. Further, both mBChE and hBChE demonstrated substrate activation for all of the examined substrates [(-)-cocaine, ACh and BTC] at high concentrations, whereas both mCocH and hCocH showed substrate inhibition for all three substrates at high concentrations. The amino-acid mutations have remarkably converted substrate activation of the enzymes into substrate inhibition, implying that the rate-determining step of the reaction in mCocH and hCocH might be different from that in mBChE and hBChE.
ESTHER : Chen_2015_Biochem.J_466_243
PubMedSearch : Chen_2015_Biochem.J_466_243
PubMedID: 25486543
Gene_locus related to this paper: human-BCHE

Title : Design, synthesis and preliminary structure-activity relationship investigation of nitrogen-containing chalcone derivatives as acetylcholinesterase and butyrylcholinesterase inhibitors: a further study based on Flavokawain B Mannich base derivatives - Liu_2015_J.Enzyme.Inhib.Med.Chem__1
Author(s) : Liu H , Fan H , Gao X , Huang X , Liu X , Liu L , Zhou C , Tang J , Wang Q , Liu W
Ref : J Enzyme Inhib Med Chem , :1 , 2015
Abstract : In order to study the structure-activity relationship of Flavokawain B Mannich-based derivatives as acetylcholinesterase (AChE) inhibitors in our recent investigation, 20 new nitrogen-containing chalcone derivatives (4 a-8d) were designed, synthesized, and evaluated for AChE inhibitory activity in vitro. The results suggested that amino alkyl side chain of chalcone dramatically influenced the inhibitory activity against AChE. Among them, compound 6c revealed the strongest AChE inhibitory activity (IC50 value: 0.85 mumol/L) and the highest selectivity against AChE over BuChE (ratio: 35.79). Enzyme kinetic study showed that the inhibition mechanism of compound 6c against AChE was a mixed-type inhibition. The molecular docking assay showed that this compound can both bind with the catalytic site and the peripheral site of AChE.
ESTHER : Liu_2015_J.Enzyme.Inhib.Med.Chem__1
PubMedSearch : Liu_2015_J.Enzyme.Inhib.Med.Chem__1
PubMedID: 26186269

Title : Genome sequence of the Asian Tiger mosquito, Aedes albopictus, reveals insights into its biology, genetics, and evolution - Chen_2015_Proc.Natl.Acad.Sci.U.S.A_112_E5907
Author(s) : Chen XG , Jiang X , Gu J , Xu M , Wu Y , Deng Y , Zhang C , Bonizzoni M , Dermauw W , Vontas J , Armbruster P , Huang X , Yang Y , Zhang H , He W , Peng H , Liu Y , Wu K , Chen J , Lirakis M , Topalis P , Van Leeuwen T , Hall AB , Thorpe C , Mueller RL , Sun C , Waterhouse RM , Yan G , Tu ZJ , Fang X , James AA
Ref : Proc Natl Acad Sci U S A , 112 :E5907 , 2015
Abstract : The Asian tiger mosquito, Aedes albopictus, is a highly successful invasive species that transmits a number of human viral diseases, including dengue and Chikungunya fevers. This species has a large genome with significant population-based size variation. The complete genome sequence was determined for the Foshan strain, an established laboratory colony derived from wild mosquitoes from southeastern China, a region within the historical range of the origin of the species. The genome comprises 1,967 Mb, the largest mosquito genome sequenced to date, and its size results principally from an abundance of repetitive DNA classes. In addition, expansions of the numbers of members in gene families involved in insecticide-resistance mechanisms, diapause, sex determination, immunity, and olfaction also contribute to the larger size. Portions of integrated flavivirus-like genomes support a shared evolutionary history of association of these viruses with their vector. The large genome repertory may contribute to the adaptability and success of Ae. albopictus as an invasive species.
ESTHER : Chen_2015_Proc.Natl.Acad.Sci.U.S.A_112_E5907
PubMedSearch : Chen_2015_Proc.Natl.Acad.Sci.U.S.A_112_E5907
PubMedID: 26483478
Gene_locus related to this paper: aedae-q177c7 , aedal-a0a182gwe3 , aedal-a0a182gwt8 , aedal-a0a023eq67

Title : Modeling in vitro inhibition of butyrylcholinesterase using molecular docking, multi-linear regression and artificial neural network approaches - Zheng_2014_Bioorg.Med.Chem_22_538
Author(s) : Zheng F , Zhan M , Huang X , Abdul Hameed MD , Zhan CG
Ref : Bioorganic & Medicinal Chemistry , 22 :538 , 2014
Abstract : Butyrylcholinesterase (BChE) has been an important protein used for development of anti-cocaine medication. Through computational design, BChE mutants with approximately 2000-fold improved catalytic efficiency against cocaine have been discovered in our lab. To study drug-enzyme interaction it is important to build mathematical model to predict molecular inhibitory activity against BChE. This report presents a neural network (NN) QSAR study, compared with multi-linear regression (MLR) and molecular docking, on a set of 93 small molecules that act as inhibitors of BChE by use of the inhibitory activities (pIC50 values) of the molecules as target values. The statistical results for the linear model built from docking generated energy descriptors were: r(2)=0.67, rmsd=0.87, q(2)=0.65 and loormsd=0.90; the statistical results for the ligand-based MLR model were: r(2)=0.89, rmsd=0.51, q(2)=0.85 and loormsd=0.58; the statistical results for the ligand-based NN model were the best: r(2)=0.95, rmsd=0.33, q(2)=0.90 and loormsd=0.48, demonstrating that the NN is powerful in analysis of a set of complicated data. As BChE is also an established drug target to develop new treatment for Alzheimer's disease (AD). The developed QSAR models provide tools for rationalizing identification of potential BChE inhibitors or selection of compounds for synthesis in the discovery of novel effective inhibitors of BChE in the future.
ESTHER : Zheng_2014_Bioorg.Med.Chem_22_538
PubMedSearch : Zheng_2014_Bioorg.Med.Chem_22_538
PubMedID: 24290065

Title : Acetylcholinesterase-catalyzed hydrolysis allows ultrasensitive detection of pathogens with the naked eye - Liu_2013_Angew.Chem.Int.Ed.Engl_52_14065
Author(s) : Liu D , Wang Z , Jin A , Huang X , Sun X , Wang F , Yan Q , Ge S , Xia N , Niu G , Liu G , Hight Walker AR , Chen X
Ref : Angew Chem Int Ed Engl , 52 :14065 , 2013
Abstract : Seeing is believing: A rapid diagnostic platform for pathogen detection based on the acetylcholinesterase-catalyzed hydrolysis reaction has been developed. Owing to signal amplification strategies, the sensitivity of this assay is comparable to that of PCR. In addition, the readout of the assay is based on solution color change, which can be easily observed by the naked eye alone.
ESTHER : Liu_2013_Angew.Chem.Int.Ed.Engl_52_14065
PubMedSearch : Liu_2013_Angew.Chem.Int.Ed.Engl_52_14065
PubMedID: 24155243

Title : Structural modifications to tetrahydropyridine-3-carboxylate esters en route to the discovery of M5-preferring muscarinic receptor orthosteric antagonists - Zheng_2013_J.Med.Chem_56_1693
Author(s) : Zheng G , Smith AM , Huang X , Subramanian KL , Siripurapu KB , Deaciuc A , Zhan CG , Dwoskin LP
Ref : Journal of Medicinal Chemistry , 56 :1693 , 2013
Abstract : The M5 muscarinic acetylcholine receptor is suggested to be a potential pharmacotherapeutic target for the treatment of drug abuse. We describe herein the discovery of a series of M5-preferring orthosteric antagonists based on the scaffold of 1,2,5,6-tetrahydropyridine-3-carboxylic acid. Compound 56, the most selective compound in this series, possesses an 11-fold selectivity for the M5 over M1 receptor and shows little activity at M2-M4. This compound, although exhibiting modest affinity (K(i) = 2.24 muM) for the [(3)H]N-methylscopolamine binding site on the M5 receptor, is potent (IC50 = 0.45 nM) in inhibiting oxotremorine-evoked [(3)H]DA release from rat striatal slices. Further, a homology model of human M5 receptor based on the crystal structure of the rat M3 receptor was constructed, and docking studies of compounds 28 and 56 were performed in an attempt to understand the possible binding mode of these novel analogues to the receptor.
ESTHER : Zheng_2013_J.Med.Chem_56_1693
PubMedSearch : Zheng_2013_J.Med.Chem_56_1693
PubMedID: 23379472

Title : Choline acetate enhanced the catalytic performance of Candida rogusa lipase in AOT reverse micelles - Xue_2013_Colloids.Surf.B.Biointerfaces_105C_81
Author(s) : Xue L , Zhao Y , Yu L , Sun Y , Yan K , Li Y , Huang X , Qu Y
Ref : Colloids Surf B Biointerfaces , 105C :81 , 2013
Abstract : Choline acetate is an ionic liquid composed of a kosmotropic anion and a chaotropic cation. According to Hofmeister series, a kosmotropic anion and/or a chaotropic cation could stabilize an enzyme, thereby facilitating the retention of the catalytic activity of the enzyme. In this work, we first report the influence of choline acetate on the activity and stability of lipase in AOT/water/isooctane reverse micelles. The indicator reaction is the lipase-catalyzed hydrolysis of 4-nitrophenyl butyrate. The results show that a low level of choline acetate does not affect the microstructure of the AOT reverse micelles, but the ionic liquid can improve the catalytic efficiency of lipase. Fluorescence spectra show that a high level of choline acetate has an impact on the conformation of lipase, so the activation is mainly due to the influence of choline acetate on the nucleophilicity of water. Infrared spectra demonstrate that choline acetate can form stronger hydrogen bonds with water surrounding lipase, and therefore enhance the nucleophilicity of the water, which makes it easier to attack the acyl enzyme intermediate, thereby increasing the activity of the lipase-catalyzed hydrolysis of the ester. A study on the stability of lipase in AOT reverse micelles indicates that the ionic liquid is able to maintain the activity of lipase to a certain extent. The effect of choline acetate is consistent with that predicted based on Hofmeister series.
ESTHER : Xue_2013_Colloids.Surf.B.Biointerfaces_105C_81
PubMedSearch : Xue_2013_Colloids.Surf.B.Biointerfaces_105C_81
PubMedID: 23352950

Title : Asperterpenols A and B, New Sesterterpenoids Isolated from a Mangrove Endophytic Fungus Aspergillus sp. 085242 - Xiao_2013_Org.Lett_15_2522
Author(s) : Xiao Z , Huang H , Shao C , Xia X , Ma L , Huang X , Lu Y , Lin Y , Long Y , She Z
Ref : Org Lett , 15 :2522 , 2013
Abstract : Asperterpenol A (1) and asperterpenol B (2), two novel sesterterpenoids with an unusual 5/8/6/6 tetracyclic ring skeleton, were isolated from a mangrove endophytic fungus Aspergillus sp. 085242. The structures were elucidated on the basis of spectroscopic methods and the absolute configurations determined by single-crystal X-ray diffraction analysis. Compounds 1 and 2 inhibit acetylcholinesterase with IC50 values of 2.3 and 3.0 muM, respectively.
ESTHER : Xiao_2013_Org.Lett_15_2522
PubMedSearch : Xiao_2013_Org.Lett_15_2522
PubMedID: 23642191

Title : A New Anti-acetylcholinesterase alpha-Pyrone Meroterpene, Arigsugacin I, from Mangrove Endophytic Fungus Penicillium sp. sk5GW1L of Kandelia candel - Huang_2013_Planta.Med_79_1572
Author(s) : Huang X , Sun X , Ding B , Lin M , Liu L , Huang H , She Z
Ref : Planta Med , 79 :1572 , 2013
Abstract : Arigsugacin I (1), a new alpha-pyrone meroterpene, along with two known compounds, arigsugacins F (2) and territrem B (3), were isolated from the mangrove endophytic fungus Penicillium sp. sk5GW1L from Kandelia candel. Their structures were identified through mass spectrometry and NMR experiments, and the absolute configuration of compound 1 was further confirmed by low-temperature (100 K) single crystal X-ray diffraction with Cu Kalpha radiation. The absolute configuration of compound 2 was first reported by using X-ray copper radiation. Compounds 1-3 showed inhibitory activities against acetylcholinesterase with IC50 values of 0.64 +/- 0.08 microM, 0.37 +/- 0.11 microM, and 7.03 +/- 0.20 nM, respectively.
ESTHER : Huang_2013_Planta.Med_79_1572
PubMedSearch : Huang_2013_Planta.Med_79_1572
PubMedID: 24081685

Title : Microscopic binding of M5 muscarinic acetylcholine receptor with antagonists by homology modeling, molecular docking, and molecular dynamics simulation - Huang_2012_J.Phys.Chem.B_116_532
Author(s) : Huang X , Zheng G , Zhan CG
Ref : J Phys Chem B , 116 :532 , 2012
Abstract : By performing homology modeling, molecular docking, and molecular dynamics (MD) simulations, we have developed three-dimensional (3D) structural models of the M5 muscarinic acetylcholine receptor (mAChR) and two complexes for M5 mAChR binding with antagonists SVT-40776 and solifenacin in the environment of lipid bilayer and solvent water. According to the simulated results, each of the antagonists is oriented horizontally in the binding pocket formed by transmembrane helices 2, 3, and 5-7. The cationic headgroup of each of the antagonists interacts with a negatively charged residue, Asp110, through electrostatic and hydrogen-bonding interactions. The simulated results also reveal some significant difference between the binding modes of SVT-40776 and solifenacin. In particular, SVT-40776 is persistently hydrogen bonded with the side chain of residue Tyr458, whereas solifenacin cannot form a similar hydrogen bond with residues around its carbonyl group. Such significant difference in the binding structures is consistent with the fact that SVT-40776 has a much higher binding affinity (K(d) = 0.4 nM) to M5 mAChR than that of solifenacin (K(d) = 31 nM) with the same reeptor. The calculated binding free energy change (-2.3 +/- 0.3 kcal/mol) from solifenacin to SVT-40776 is in good agreement with the experimentally derived binding free energy change (-2.58 kcal/mol), suggesting that our modeled M5 mAChR structure and its complexes with the antagonists are reliable. The new structural insights obtained from this computational study are expected to stimulate further biochemical and pharmacological studies on the detailed structures of M5 and other subtypes of mAChRs.
ESTHER : Huang_2012_J.Phys.Chem.B_116_532
PubMedSearch : Huang_2012_J.Phys.Chem.B_116_532
PubMedID: 22185605

Title : Cocaine esterase-cocaine binding process and the free energy profiles by molecular dynamics and potential of mean force simulations - Huang_2012_J.Phys.Chem.B_116_3361
Author(s) : Huang X , Zhao X , Zheng F , Zhan CG
Ref : J Phys Chem B , 116 :3361 , 2012
Abstract : The combined molecular dynamics (MD) and potential of mean force (PMF) simulations have been performed to determine the free energy profiles for the binding process of (-)-cocaine interacting with wild-type cocaine esterase (CocE) and its mutants (T172R/G173Q and L119A/L169K/G173Q). According to the MD simulations, the general protein-(-)-cocaine binding mode is not affected by the mutations; e.g.. the benzoyl group of (-)-cocaine is always bound in a subsite composed of aromatic residues W151, W166, F261, and F408 and hydrophobic residue L407, while the carbonyl oxygen on the benzoyl group of (-)-cocaine is hydrogen-bonded with the oxyanion-hole residues Y44 and Y118. According to the PMF-calculated free energy profiles for the binding process, the binding free energies for (-)-cocaine with the wild-type, T172R/G173Q, and L119A/L169K/G173Q CocEs are predicted to be -6.4, -6.2, and -5.0 kcal/mol, respectively. The computational predictions are supported by experimental kinetic data, as the calculated binding free energies are in good agreement with the experimentally derived binding free energies, i.e., -7.2, -6.7, and -4.8 kcal/mol for the wild-type, T172R/G173Q, and L119A/L169K/G173Q, respectively. The reasonable agreement between the computational and experimental data suggests that the PMF simulations may be used as a valuable tool in new CocE mutant design that aims to decrease the Michaelis-Menten constant of the enzyme for (-)-cocaine.
ESTHER : Huang_2012_J.Phys.Chem.B_116_3361
PubMedSearch : Huang_2012_J.Phys.Chem.B_116_3361
PubMedID: 22385120

Title : SulE, a sulfonylurea herbicide de-esterification esterase from Hansschlegelia zhihuaiae S113 - Hang_2012_Appl.Environ.Microbiol_78_1962
Author(s) : Hang BJ , Hong Q , Xie XT , Huang X , Wang CH , He J , Li SP
Ref : Applied Environmental Microbiology , 78 :1962 , 2012
Abstract : De-esterification is an important degradation or detoxification mechanism of sulfonylurea herbicide in microbes and plants. However, the biochemical and molecular mechanisms of sulfonylurea herbicide de-esterification are still unknown. In this study, a novel esterase gene, sulE, responsible for sulfonylurea herbicide de-esterification, was cloned from Hansschlegelia zhihuaiae S113. The gene contained an open reading frame of 1,194 bp, and a putative signal peptide at the N terminal was identified with a predicted cleavage site between Ala37 and Glu38, resulting in a 361-residue mature protein. SulE minus the signal peptide was synthesized in Escherichia coli BL21 and purified to homogeneity. SulE catalyzed the de-esterification of a variety of sulfonylurea herbicides that gave rise to the corresponding herbicidally inactive parent acid and exhibited the highest catalytic efficiency toward thifensulfuron-methyl. SulE was a dimer without the requirement of a cofactor. The activity of the enzyme was completely inhibited by Ag(+), Cd(2+), Zn(2+), methamidophos, and sodium dodecyl sulfate. A sulE-disrupted mutant strain, DeltasulE, was constructed by insertion mutation. DeltasulE lost the de-esterification ability and was more sensitive to the herbicides than the wild type of strain S113, suggesting that sulE played a vital role in the sulfonylurea herbicide resistance of the strain. The transfer of sulE into Saccharomyces cerevisiae BY4741 conferred on it the ability to de-esterify sulfonylurea herbicides and increased its resistance to the herbicides. This study has provided an excellent candidate for the mechanistic study of sulfonylurea herbicide metabolism and detoxification through de-esterification, construction of sulfonylurea herbicide-resistant transgenic crops, and bioremediation of sulfonylurea herbicide-contaminated environments.
ESTHER : Hang_2012_Appl.Environ.Microbiol_78_1962
PubMedSearch : Hang_2012_Appl.Environ.Microbiol_78_1962
PubMedID: 22247165
Gene_locus related to this paper: 9rhiz-g9i933

Title : A retrospective review of 15 patients with familial myasthenia gravis over a period of 25 years - Feng_2012_Neurol.Sci_33_771
Author(s) : Feng HY , Liu WB , Luo CM , Yang LX , Fang W , Qiu L , Huang X , Li Y , Huang RX
Ref : Neurol Sci , 33 :771 , 2012
Abstract : We observed, during a 25-year period, 15 patients from 6 families with autoimmune myasthenia gravis (all Chinese Han from Guangdong Province) referred to our department. Their mean onset age was 13.4 years (range 2-25 years) with 10 patients with juvenile onset. The female:male ratio was 3:2. Acetylcholine receptors antibody titers were increased in 11 patients (range 1.62-19.8 nmol/L). Thymectomy was performed in six patients, who received corticosteroids /immune inhibitor plus pyridostigmine treatments after surgery. The other patients were placed on therapy with azathioprine, cyclophosphamide, corticosteroids and acetylcholinesterase inhibitors. All patients responded well to immunosuppressants, and psychiatric symptoms were observed only in one patient who received a high dose of corticosteroids. Patients with generalized type in the same family had different presentations with variable prognosis. HLA-A 0207 was found in 9 patients (9/15), HLA-B 4601 in 11 patients (11/15), and HLA-DRB1 0901 in 12 patients (12/15). When compared to familial autoimmune myasthenia gravis in other countries, we observed peculiar characteristics of Chinese populations, such as the within-family consistency was only found in families with ocular MG type (50% of all MG families), while the pathogenetic conditions and the prognoses of the generalized MG patients may differ greatly within the same family. These findings may shed new light on the genetic predisposition and the origin of immune abnormalities of MG patients.
ESTHER : Feng_2012_Neurol.Sci_33_771
PubMedSearch : Feng_2012_Neurol.Sci_33_771
PubMedID: 22057263

Title : Beta-secretase inhibitor GRL-8234 rescues age-related cognitive decline in APP transgenic mice - Chang_2011_FASEB.J_25_775
Author(s) : Chang WP , Huang X , Downs D , Cirrito JR , Koelsch G , Holtzman DM , Ghosh AK , Tang J
Ref : FASEB Journal , 25 :775 , 2011
Abstract : Alzheimer disease is intimately linked to an excess amount of amyloid-beta (Abeta) in the brain. Thus, therapeutic inhibition of Abeta production is an attractive clinical approach to treat this disease. Here we provide the first direct experimental evidence that the treatment of Tg2576 transgenic mice with an inhibitor of beta-secretase, GRL-8234, rescues the age-related cognitive decline. We demonstrated that the injected GRL-8234 effectively enters the brain and rapidly decreases soluble Abeta in the brain of Tg2576 mice. The rescue of cognition, which was observed only after long-term inhibitor treatment ranging from 5 to 7.5 mo, was associated with a decrease of brain amyloid-beta plaque load. We also found no accumulation of amyloid-beta precursor protein after several months of inhibitor treatment. These observations substantiate the idea that Abeta accumulation plays a major role in the cognitive decline of Tg2576 mice and support the concept of Abeta reduction therapy as a treatment of AD.
ESTHER : Chang_2011_FASEB.J_25_775
PubMedSearch : Chang_2011_FASEB.J_25_775
PubMedID: 21059748

Title : Computational design of a thermostable mutant of cocaine esterase via molecular dynamics simulations - Huang_2011_Org.Biomol.Chem_9_4138
Author(s) : Huang X , Gao D , Zhan CG
Ref : Org Biomol Chem , 9 :4138 , 2011
Abstract : Cocaine esterase (CocE) has been known as the most efficient native enzyme for metabolizing naturally occurring cocaine. A major obstacle to the clinical application of CocE is the thermoinstability of native CocE with a half-life of only approximately 11 min at physiological temperature (37 degrees C). It is highly desirable to develop a thermostable mutant of CocE for therapeutic treatment of cocaine overdose and addiction. To establish a structure-thermostability relationship, we carried out molecular dynamics (MD) simulations at 400 K on wild-type CocE and previously known thermostable mutants, demonstrating that the thermostability of the active form of the enzyme correlates with the fluctuation (characterized as the root-mean square deviation and root-mean square fluctuation of atomic positions) of the catalytic residues (Y44, S117, Y118, H287, and D259) in the simulated enzyme. In light of the structure-thermostability correlation, further computational modelling including MD simulations at 400 K predicted that the active site structure of the L169K mutant should be more thermostable. The prediction has been confirmed by wet experimental tests showing that the active form of the L169K mutant had a half-life of 570 min at 37 degrees C, which is significantly longer than those of the wild-type and previously known thermostable mutants. The encouraging outcome suggests that the high-temperature MD simulations and the structure-thermostability relationship may be considered as a valuable tool for the computational design of thermostable mutants of an enzyme.
ESTHER : Huang_2011_Org.Biomol.Chem_9_4138
PubMedSearch : Huang_2011_Org.Biomol.Chem_9_4138
PubMedID: 21373712

Title : Genomic and proteomic analyses of the fungus Arthrobotrys oligospora provide insights into nematode-trap formation - Yang_2011_PLoS.Pathog_7_e1002179
Author(s) : Yang J , Wang L , Ji X , Feng Y , Li X , Zou C , Xu J , Ren Y , Mi Q , Wu J , Liu S , Liu Y , Huang X , Wang H , Niu X , Li J , Liang L , Luo Y , Ji K , Zhou W , Yu Z , Li G , Li L , Qiao M , Feng L , Zhang KQ
Ref : PLoS Pathog , 7 :e1002179 , 2011
Abstract : Nematode-trapping fungi are "carnivorous" and attack their hosts using specialized trapping devices. The morphological development of these traps is the key indicator of their switch from saprophytic to predacious lifestyles. Here, the genome of the nematode-trapping fungus Arthrobotrys oligospora Fres. (ATCC24927) was reported. The genome contains 40.07 Mb assembled sequence with 11,479 predicted genes. Comparative analysis showed that A. oligospora shared many more genes with pathogenic fungi than with non-pathogenic fungi. Specifically, compared to several sequenced ascomycete fungi, the A. oligospora genome has a larger number of pathogenicity-related genes in the subtilisin, cellulase, cellobiohydrolase, and pectinesterase gene families. Searching against the pathogen-host interaction gene database identified 398 homologous genes involved in pathogenicity in other fungi. The analysis of repetitive sequences provided evidence for repeat-induced point mutations in A. oligospora. Proteomic and quantitative PCR (qPCR) analyses revealed that 90 genes were significantly up-regulated at the early stage of trap-formation by nematode extracts and most of these genes were involved in translation, amino acid metabolism, carbohydrate metabolism, cell wall and membrane biogenesis. Based on the combined genomic, proteomic and qPCR data, a model for the formation of nematode trapping device in this fungus was proposed. In this model, multiple fungal signal transduction pathways are activated by its nematode prey to further regulate downstream genes associated with diverse cellular processes such as energy metabolism, biosynthesis of the cell wall and adhesive proteins, cell division, glycerol accumulation and peroxisome biogenesis. This study will facilitate the identification of pathogenicity-related genes and provide a broad foundation for understanding the molecular and evolutionary mechanisms underlying fungi-nematodes interactions.
ESTHER : Yang_2011_PLoS.Pathog_7_e1002179
PubMedSearch : Yang_2011_PLoS.Pathog_7_e1002179
PubMedID: 21909256
Gene_locus related to this paper: artoa-g1wyr4 , artoa-g1x1a7 , artoa-g1x3f4 , artoa-g1x3h6 , artoa-g1x9s5 , artoa-g1x9z4 , artoa-g1xcb5 , artoa-g1xhl6 , artoa-g1xjb3 , artoa-g1xjy0 , artoa-g1xkw3 , artoa-g1xnf2 , artoa-g1xnf8 , artoa-g1xqd4 , artoa-g1xqt1 , artoa-g1xte8 , artoa-g1xu91 , artoa-g1xv59 , artoa-g1x382 , artoa-g1x3q3 , artoa-g1wxl5 , artoa-g1xj75 , artoa-g1xd25 , artoa-g1wzu7 , artoa-g1xt42 , artoa-g1xhm8 , artoa-g1wy43

Title : Human butyrylcholinesterase-cocaine binding pathway and free energy profiles by molecular dynamics and potential of mean force simulations - Huang_2011_J.Phys.Chem.B_115_11254
Author(s) : Huang X , Zheng F , Zhan CG
Ref : J Phys Chem B , 115 :11254 , 2011
Abstract : In the present study, we have performed combined molecular dynamics and potential of mean force (PMF) simulations to determine the enzyme-substrate (ES) binding pathway and the corresponding free energy profiles for wild-type butyrylcholinesterase (BChE) binding with (-)/(+)-cocaine and for the A328W/Y332G mutant binding with (-)-cocaine. According to the PMF simulations, for each ES binding system, the substrate first binds with the enzyme at a peripheral anionic site around the entrance of the active-site gorge to form the first ES complex (ES1-like) during the binding process. Further evolution from the ES1-like complex to the nonprereactive ES complex is nearly barrierless, with a free energy barrier lower than 1.0 kcal/mol. So, the nonprereactive ES binding process should be very fast. The rate-determining step of the entire ES binding process is the subsequent evolution from the nonprereactive ES complex to the prereactive ES complex. Further accounting for the entire ES binding process, the PMF-based simulations qualitatively reproduced the relative order of the experimentally derived binding free energies (DeltaG(bind)), although the simulations systematically overestimated the magnitude of the binding affinity and systematically underestimated the differences between the DeltaG(bind) values. The obtained structural and energetic insights into the entire ES binding process provide a valuable base for future rational design of high-activity mutants of BChE as candidates for an enzyme therapy for cocaine overdose and abuse.
ESTHER : Huang_2011_J.Phys.Chem.B_115_11254
PubMedSearch : Huang_2011_J.Phys.Chem.B_115_11254
PubMedID: 21902185

Title : Genomic analysis and temperature-dependent transcriptome profiles of the rhizosphere originating strain Pseudomonas aeruginosa M18 - Wu_2011_BMC.Genomics_12_438
Author(s) : Wu DQ , Ye J , Ou HY , Wei X , Huang X , He YW , Xu Y
Ref : BMC Genomics , 12 :438 , 2011
Abstract : BACKGROUND: Our previously published reports have described an effective biocontrol agent named Pseudomonas sp. M18 as its 16S rDNA sequence and several regulator genes share homologous sequences with those of P. aeruginosa, but there are several unusual phenotypic features. This study aims to explore its strain specific genomic features and gene expression patterns at different temperatures.
RESULTS: The complete M18 genome is composed of a single chromosome of 6,327,754 base pairs containing 5684 open reading frames. Seven genomic islands, including two novel prophages and five specific non-phage islands were identified besides the conserved P. aeruginosa core genome. Each prophage contains a putative chitinase coding gene, and the prophage II contains a capB gene encoding a putative cold stress protein. The non-phage genomic islands contain genes responsible for pyoluteorin biosynthesis, environmental substance degradation and type I and III restriction-modification systems. Compared with other P. aeruginosa strains, the fewest number (3) of insertion sequences and the most number (3) of clustered regularly interspaced short palindromic repeats in M18 genome may contribute to the relative genome stability. Although the M18 genome is most closely related to that of P. aeruginosa strain LESB58, the strain M18 is more susceptible to several antimicrobial agents and easier to be erased in a mouse acute lung infection model than the strain LESB58. The whole M18 transcriptomic analysis indicated that 10.6% of the expressed genes are temperature-dependent, with 22 genes up-regulated at 28 degrees C in three non-phage genomic islands and one prophage but none at 37 degrees C.
CONCLUSIONS: The P. aeruginosa strain M18 has evolved its specific genomic structures and temperature dependent expression patterns to meet the requirement of its fitness and competitiveness under selective pressures imposed on the strain in rhizosphere niche.
ESTHER : Wu_2011_BMC.Genomics_12_438
PubMedSearch : Wu_2011_BMC.Genomics_12_438
PubMedID: 21884571
Gene_locus related to this paper: pseae-PA1558 , pseae-PA2927 , pseae-PA2949 , pseae-PA3695 , pseae-PA5080 , pseae-q9i252

Title : Synthesis of 2-(substituted phenyl)-3,5,5-trimethylmorpholine analogues and their effects on monoamine uptake, nicotinic acetylcholine receptor function, and behavioral effects of nicotine - Carroll_2011_J.Med.Chem_54_1441
Author(s) : Carroll FI , Muresan AZ , Blough BE , Navarro HA , Mascarella SW , Eaton JB , Huang X , Damaj MI , Lukas RJ
Ref : Journal of Medicinal Chemistry , 54 :1441 , 2011
Abstract : Toward development of smoking cessation aids superior to bupropion (2), we describe synthesis of 2-(substituted phenyl)-3,5,5-trimethylmorpholine analogues 5a-5h and their effects on inhibition of dopamine, norepinephrine, and serotonin uptake, nicotinic acetylcholine receptor (nAChR) function, acute actions of nicotine, and nicotine-conditioned place preference (CPP). Several analogues encompassing aryl substitutions, N-alkylation, and alkyl extensions of the morpholine ring 3-methyl group provided analogues more potent in vitro than (S,S)-hydroxybupropion (4a) as inhibitors of dopamine or norepinephrine uptake and antagonists of nAChR function. All of the new (S,S)-5 analogues had better potency than (S,S)-4a as blockers of acute nicotine analgesia in the tail-flick test. Two analogues with highest potency at alpha3beta4*-nAChR and among the most potent transporter inhibitors have better potency than (S,S)-4a in blocking nicotine-CPP. Collectively, these findings illuminate mechanisms of action of 2 analogues and identify deshydroxybupropion analogues 5a-5h as possibly superior candidates as aids to smoking cessation.
ESTHER : Carroll_2011_J.Med.Chem_54_1441
PubMedSearch : Carroll_2011_J.Med.Chem_54_1441
PubMedID: 21319801

Title : Smoking duration, intensity, and risk of Parkinson disease - Chen_2010_Neurology_74_878
Author(s) : Chen H , Huang X , Guo X , Mailman RB , Park Y , Kamel F , Umbach DM , Xu Q , Hollenbeck A , Schatzkin A , Blair A
Ref : Neurology , 74 :878 , 2010
Abstract : OBJECTIVE: To evaluate the relative importance of smoking duration vs intensity in reducing the risk of Parkinson disease (PD).
METHODS: The study included 305,468 participants of the NIH-AARP Diet and Health cohort, of whom 1,662 had a PD diagnosis after 1995. We estimated odds ratios (OR) and 95% confidence intervals from multivariate logistic regression models.
RESULTS: Compared with never smokers, the multivariate ORs were 0.78 for past smokers and 0.56 for current smokers. Among past smokers, a monotonic trend toward lower PD risk was observed for all indicators of more smoking. Stratified analyses indicated that smoking duration was associated with lower PD risk within fixed intensities of smoking. For example, compared with never smokers, the ORs among past smokers who smoked >20 cigarettes/day were 0.96 for 1-9 years of smoking, 0.78 for 10-19 years, 0.64 for 20-29 years, and 0.59 for 30 years or more (p for trend = 0.001). In contrast, at fixed duration, the typical number of cigarettes smoked per day in general was not related to PD risk. Close examination of smoking behaviors in early life showed that patients with PD were less likely to be smokers at each age period, but if they smoked, they smoked similar numbers of cigarettes per day as individuals without PD.
CONCLUSIONS: This large study suggests that long-term smoking is more important than smoking intensity in the smoking-Parkinson disease relationship.
ESTHER : Chen_2010_Neurology_74_878
PubMedSearch : Chen_2010_Neurology_74_878
PubMedID: 20220126

Title : Synthesis and characterization of in vitro and in vivo profiles of hydroxybupropion analogues: aids to smoking cessation - Lukas_2010_J.Med.Chem_53_4731
Author(s) : Lukas RJ , Muresan AZ , Damaj MI , Blough BE , Huang X , Navarro HA , Mascarella SW , Eaton JB , Marxer-Miller SK , Carroll FI
Ref : Journal of Medicinal Chemistry , 53 :4731 , 2010
Abstract : To create potentially superior aids to smoking cessation and/or antidepressants and to elucidate bupropion's possible mechanisms of action(s), 23 analogues based on its active hydroxymetabolite (2S,3S)-4a were synthesized and tested for their abilities to inhibit monoamine uptake and nAChR subtype activities in vitro and acute effects of nicotine in vivo. The 3',4'-dichlorophenyl [(+/-)-4n], naphthyl (4r), and 3-chlorophenyl or 3-propyl analogues 4s and 4t, respectively, had higher inhibitory potency and/or absolute selectivity than (2S,3S)-4a for inhibition of DA, NE, or 5HT uptake. The 3'-fluorophenyl, 3'-bromophenyl, and 4-biphenyl analogues 4c, 4d, and 4l, respectively, had higher potency for antagonism of alpha4beta2-nAChR than (2S,3S)-4a. Several analogues also had higher potency than (2S,3S)-4a as antagonists of nicotine-mediated antinociception in the tail-flick assay. The results suggest that compounds acting via some combination of DA, NE, or 5HT inhibition and/or antagonism of alpha4beta2-nAChR can potentially be new pharmacotherapeutics for treatment of nicotine dependence.
ESTHER : Lukas_2010_J.Med.Chem_53_4731
PubMedSearch : Lukas_2010_J.Med.Chem_53_4731
PubMedID: 20509659

Title : The Arabidopsis LSD1 gene plays an important role in the regulation of low temperature-dependent cell death - Huang_2010_New.Phytol_187_301
Author(s) : Huang X , Li Y , Zhang X , Zuo J , Yang S
Ref : New Phytol , 187 :301 , 2010
Abstract : SUMMARY: In higher plants, the crosstalk between cold stress responses and reactive oxygen species (ROS) signaling is not well understood. *Two chilling-sensitive mutants, chs4-1 and chs4-3, were characterized genetically and molecularly. *The CHS4 gene, identified by map-based cloning, was found to be identical to lesion simulating disease resistance 1 (LSD1). We therefore renamed these two alleles lsd1-3 and lsd1-4, respectively. These two mutants exhibited an extensive cell death phenotype under cold stress conditions. Consistently, lsd1-3 plants exposed to cold showed up-regulation of the PR1 and PR2 genes, and increased accumulation of salicylic acid. These results indicate that low temperature is another trigger of cell death in lsd1 mutants. Furthermore, lsd1-3 plants accumulated higher concentrations of H(2)O(2) and total glutathione under cold conditions than wild-type plants. Genetic analysis revealed that PAD4 and EDS1, two key signaling regulators mediating resistance responses, are required for the chilling-sensitive phenotype of lsd1-3. *These findings reveal a role of LSD1 in regulating cell death trigged by cold stress and a link between cold stress responses and ROS-associated signaling.
ESTHER : Huang_2010_New.Phytol_187_301
PubMedSearch : Huang_2010_New.Phytol_187_301
PubMedID: 20456049

Title : Reaction pathway and free energy profile for prechemical reaction step of human butyrylcholinesterase-catalyzed hydrolysis of (-)-cocaine by combined targeted molecular dynamics and potential of mean force simulations - Huang_2010_J.Phys.Chem.B_114_13545
Author(s) : Huang X , Pan Y , Zheng F , Zhan CG
Ref : J Phys Chem B , 114 :13545 , 2010
Abstract : Combined targeted molecular dynamics (TMD) and potential of mean force (PMF) simulations have been carried out to uncover the detailed pathway and determine the corresponding free energy profile for the structural transformation from the nonprereactive butyrylcholinesterase (BChE)-(-)-cocaine binding to the prereactive BChE-(-)-cocaine binding associated with the (-)-cocaine rotation in the binding pocket of BChE. It has been shown that the structural transformation involves two transition states (TS1(rot) and TS2(rot)). TS1(rot) is mainly associated with the deformation of the nonprereactive complex, whereas TS2(rot) is mainly associated with the formation of the prereactive complex. It has also been demonstrated that the A328W/Y332G mutation significantly reduces the steric hindrance for (-)-cocaine rotation in the binding pocket of BChE and, thus, decreases the free energy barrier for the structural transformation from the nonprereactive binding to the prereactive binding. The calculated relative free energy barriers are all consistent with available experimental kinetic data. The new mechanistic insights obtained and the novel computational protocol tested in this study should be valuable for future computational design of high-activity mutants of BChE. The general computational strategy and approach based on the combined TMD and PMF simulations may be also valuable in computational studies of detailed pathways and free energy profiles for other similar mechanistic problems involving ligand rotation or another type of structural transformation in the binding pocket of a protein.
ESTHER : Huang_2010_J.Phys.Chem.B_114_13545
PubMedSearch : Huang_2010_J.Phys.Chem.B_114_13545
PubMedID: 20883001

Title : Depression and the subsequent risk of Parkinson's disease in the NIH-AARP Diet and Health Study - Fang_2010_Mov.Disord_25_1157
Author(s) : Fang F , Xu Q , Park Y , Huang X , Hollenbeck A , Blair A , Schatzkin A , Kamel F , Chen H
Ref : Movement Disorders , 25 :1157 , 2010
Abstract : We conducted a case-control study to examine the association between depression and Parkinson's disease (PD). Participants included 992 PD cases diagnosed after 2,000 and 279,958 individuals without PD from the NIH-AARP Diet and Health Study follow-up survey. Physician-diagnosed depression and PD were self-reported with information on the year of diagnosis in the following categories: before 1985, 1985-1994, 1995-1999, and 2000-present. Only PD cases diagnosed after 2000 were included in the analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived from logistic regression models, adjusted for age, gender, educational level, marital status, smoking, and coffee drinking. Individuals with depression diagnosed after 2000 were more likely to report a concurrent diagnosis of PD than those without depression (OR = 4.7, 95% CI = 3.9, 5.7). Depression diagnosed before 2000 was also associated with higher odds of PD diagnosed after 2000 (OR = 2.0, 95% CI = 1.6, 2.4). This association was stronger for depression diagnosed in 1995-1999 (OR = 2.7, 95% CI = 2.0, 3.6), but was also noted for depression diagnosed in 1985-1994 (OR = 1.6, 95% CI = 1.1, 2.3) or even before 1985 (OR = 1.7, 95% CI = 1.3, 2.3). This association was not modified by other factors and persisted in an analysis excluding participants who reported poor health status. The results suggest that depression may either be a very early symptom of PD or share common etiological factors with PD.
ESTHER : Fang_2010_Mov.Disord_25_1157
PubMedSearch : Fang_2010_Mov.Disord_25_1157
PubMedID: 20310050

Title : [Effects of lipoprotein lipase gene Ser447stop polymorphism on changes of serum lipid ratios induced by high-carbohydrate\/low-fat diet in healthy youth] - Huang_2010_Sichuan.Da.Xue.Xue.Bao.Yi.Xue.Ban_41_243
Author(s) : Huang X , Fang DZ , Du J , Tang H , Li RH
Ref : Sichuan Da Xue Xue Bao Yi Xue Ban , 41 :243 , 2010
Abstract : OBJECTIVE To investigate the effects of lipoprotein lipase gene (LPL) Ser447stop polymorphism on serum lipid ratios and their responses to high-carbohydrate/low-fat (HC/LF) diet in healthy youth. METHODS: Fifty-six healthy subjects [(22.89 +/- 1.80) years) were given control diets of 31% fat and 54% carbohydrate for 7 days, followed by HC diets of 15% fat and 70% carbohydrate for 6 days, without total energy restriction. Serum lipid profiles at baseline, before and after HC diets, as well as LPL Ser447stop polymorphisms were analyzed. TG/ HDL-C, log (TG/HDL-C), TC/HDL-C, and LDL-C/HDL-C were calculated. RESULTS: No significant differences were found of the lipid ratios at baseline and before and after HC/LF diet between subjects of wild type (S447S) and mutation carriers (447XC) in the whole study population or males and females separately. When compared with those before HC/LF diet, significantly decreased LDL-C/HDL-C and TC/HDL-C were found regardless of LPL Ser447stop genotype (P < 0.05) and increased log (TG/HDL-C) in subjects with S447S (P < 0.05) in the whole study population. After gender was taken into account, LDL-C/HDL-C and TC/HDL-C were significantly decreased in males (P < 0.001) regardless of LPL Ser447stop polymorphism. TG/HDL-C and log (TG/HDL-C) were significantly increased (P < 0.05), and LDL-C/HDL-C and TC/HDL-C were significantly decreased (P < 0.05) in females with S447S. No significant differences were found in females with 447XC. CONCLUSION: The functional C to G mutation of LPL Ser447Stop could attenuate the elevated log (TG/HDL-C) induced by HC/LF diet. Interactions of LPL Ser447Stop polymorphism with HC/LF diet on the lipid ratios were gender-specific and effective only in females.
ESTHER : Huang_2010_Sichuan.Da.Xue.Xue.Bao.Yi.Xue.Ban_41_243
PubMedSearch : Huang_2010_Sichuan.Da.Xue.Xue.Bao.Yi.Xue.Ban_41_243
PubMedID: 20506644

Title : A gold nanoparticle labeling strategy for the sensitive kinetic assay of the carbamate-acetylcholinesterase interaction by surface plasmon resonance - Huang_2009_Talanta_78_1036
Author(s) : Huang X , Tu H , Zhu D , Du D , Zhang A
Ref : Talanta , 78 :1036 , 2009
Abstract : The article presents a novel strategy for a sensitive investigation of the interaction between acetylcholinesterase (AChE) and its small molecular carbamate inhibitors. Two carbamate inhibitors with different ether linkages and the terminal lipoate were synthesized and labeled with gold nanoparticles (AuNPs). With the signal amplification of AuNPs, the specific interactions between the AuNPs labeled carbamate inhibitors (ALC1 and ALC2) and the immobilized AChE on sensor chip surface were readily examined. The detection sensitivities of ALC1 and ALC2 were 176 and 121 m degrees /nM, respectively, with the detection limits of 7.0 and 12pM at a signal-to-noise ratio of 3. The association/dissociation constants for the binding interaction between carbamate inhibitors and AChE were reported for the first time. The affinity constants were estimated to be 3.13 x 10(6) and 6.39 x 10(5)M(-1) for ALC1 and ALC2 respectively. This AuNPs labeling strategy is versatile and may be applicable for the direct or competitive SPR kinetic assay of the interaction between small molecule inhibitors and their target proteins with a high sensitivity.
ESTHER : Huang_2009_Talanta_78_1036
PubMedSearch : Huang_2009_Talanta_78_1036
PubMedID: 19269469

Title : Cloning and expression of lipP, a gene encoding a cold-adapted lipase from Moritella sp.2-5-10-1 - Yang_2008_Curr.Microbiol_56_194
Author(s) : Yang X , Lin X , Fan T , Bian J , Huang X
Ref : Curr Microbiol , 56 :194 , 2008
Abstract : A gene (lipP, 837 bp in length) coding for a cold-adapted lipase of psychrophilic bacterium Moritella sp. 2-5-10-1 isolated from Antarctic region was cloned and sequenced in this study. The deduced amino acid sequence revealed a protein of 278 amino acid residues with a molecular mass of 30,521. The primary structure of the lipase deduced from the nucleotide sequence showed consensus pentapeptide containing the active serine [Gly-Trp-Ser-Leu-Gly] and a conserved His-Gly dipeptide in the N-terminal part of the enzyme. These sequences were involved in the lipase active site conformation. Structure factors that would allow proper enzyme flexibility at low temperatures were discussed. It was suggested that the changes in the primary structure of the psychrophilic lipases compared to the thermophilic ones could account for their ability to catalyze lipolysis at temperatures close to 0 degrees C. For expression, the sequence corresponding to the cold-adapted lipase of strain 2-5-10-1 was subcloned into the pET-28a expression vector to construct a recombinant lipase protein. Expression of the lipase by Escherichia coli BL21 (DE3) cells was observed as clear halos on 1% (vol/vol) tributyrin upon induction with IPTG at 25 degrees C.
ESTHER : Yang_2008_Curr.Microbiol_56_194
PubMedSearch : Yang_2008_Curr.Microbiol_56_194
PubMedID: 17973159

Title : Modeling binding modes of alpha7 nicotinic acetylcholine receptor with ligands: the roles of Gln117 and other residues of the receptor in agonist binding - Huang_2008_J.Med.Chem_51_6293
Author(s) : Huang X , Zheng F , Stokes C , Papke RL , Zhan CG
Ref : Journal of Medicinal Chemistry , 51 :6293 , 2008
Abstract : Extensive molecular docking, molecular dynamics simulations, and binding free energy calculations have been performed to understand how alpha7-specific agonists of nicotinic acetylcholine receptor (nAChR), including AR-R17779 (1), GTS-21 (4), and 4-OH-GTS-21 (5), interact with the alpha7 receptor, leading to important new insights into the receptor-agonist binding. In particular, the cationic head of 4 and 5 has favorable hydrogen bonding and cation-pi interactions with residue Trp149. The computational results have also led us to better understand the roles of Gln117 and other residues in the receptor binding with agonists. The computational predictions are supported by data obtained from wet experimental tests. The new insights into the binding and structure-activity relationship obtained from this study should be valuable for future rational design of more potent and selective agonists of the alpha7 receptor.
ESTHER : Huang_2008_J.Med.Chem_51_6293
PubMedSearch : Huang_2008_J.Med.Chem_51_6293
PubMedID: 18826295

Title : Genome analysis of the platypus reveals unique signatures of evolution - Warren_2008_Nature_453_175
Author(s) : Warren WC , Hillier LW , Marshall Graves JA , Birney E , Ponting CP , Grutzner F , Belov K , Miller W , Clarke L , Chinwalla AT , Yang SP , Heger A , Locke DP , Miethke P , Waters PD , Veyrunes F , Fulton L , Fulton B , Graves T , Wallis J , Puente XS , Lopez-Otin C , Ordonez GR , Eichler EE , Chen L , Cheng Z , Deakin JE , Alsop A , Thompson K , Kirby P , Papenfuss AT , Wakefield MJ , Olender T , Lancet D , Huttley GA , Smit AF , Pask A , Temple-Smith P , Batzer MA , Walker JA , Konkel MK , Harris RS , Whittington CM , Wong ES , Gemmell NJ , Buschiazzo E , Vargas Jentzsch IM , Merkel A , Schmitz J , Zemann A , Churakov G , Kriegs JO , Brosius J , Murchison EP , Sachidanandam R , Smith C , Hannon GJ , Tsend-Ayush E , McMillan D , Attenborough R , Rens W , Ferguson-Smith M , Lefevre CM , Sharp JA , Nicholas KR , Ray DA , Kube M , Reinhardt R , Pringle TH , Taylor J , Jones RC , Nixon B , Dacheux JL , Niwa H , Sekita Y , Huang X , Stark A , Kheradpour P , Kellis M , Flicek P , Chen Y , Webber C , Hardison R , Nelson J , Hallsworth-Pepin K , Delehaunty K , Markovic C , Minx P , Feng Y , Kremitzki C , Mitreva M , Glasscock J , Wylie T , Wohldmann P , Thiru P , Nhan MN , Pohl CS , Smith SM , Hou S , Nefedov M , de Jong PJ , Renfree MB , Mardis ER , Wilson RK
Ref : Nature , 453 :175 , 2008
Abstract : We present a draft genome sequence of the platypus, Ornithorhynchus anatinus. This monotreme exhibits a fascinating combination of reptilian and mammalian characters. For example, platypuses have a coat of fur adapted to an aquatic lifestyle; platypus females lactate, yet lay eggs; and males are equipped with venom similar to that of reptiles. Analysis of the first monotreme genome aligned these features with genetic innovations. We find that reptile and platypus venom proteins have been co-opted independently from the same gene families; milk protein genes are conserved despite platypuses laying eggs; and immune gene family expansions are directly related to platypus biology. Expansions of protein, non-protein-coding RNA and microRNA families, as well as repeat elements, are identified. Sequencing of this genome now provides a valuable resource for deep mammalian comparative analyses, as well as for monotreme biology and conservation.
ESTHER : Warren_2008_Nature_453_175
PubMedSearch : Warren_2008_Nature_453_175
PubMedID: 18464734
Gene_locus related to this paper: ornan-f6s0q0 , ornan-f6ty74 , ornan-f6u2k2 , ornan-f6uve1 , ornan-f6vpb6 , ornan-f6ybp3 , ornan-f7bgu8 , ornan-f7ct41 , ornan-f7cza1 , ornan-f7ejp8 , ornan-f7exu1 , ornan-f7f392 , ornan-f7f9y6 , ornan-f6ve87 , ornan-f7f1d9 , ornan-f6z3l1 , ornan-f6r3f9 , ornan-f6r3g8 , ornan-f6vs71 , ornan-f7g4v8

Title : An amperometric acetylthiocholine sensor based on immobilization of acetylcholinesterase on a multiwall carbon nanotube-cross-linked chitosan composite - Du_2007_Anal.Bioanal.Chem_387_1059
Author(s) : Du D , Huang X , Cai J , Zhang A , Ding J , Chen S
Ref : Anal Bioanal Chem , 387 :1059 , 2007
Abstract : A simple method has been devised for immobilization of acetylcholinesterase (AChE)--covalent bonding to a multiwall carbon nanotube (MWNT)--cross-linked chitosan composite (CMC)-and a sensitive amperometric sensor for rapid detection of acetylthiocholine (ATCl) has been based on this. Fourier-transform infrared spectroscopy proved that the native structure of the immobilized enzyme was preserved on this chemically clean and homogeneous composite film, because of the excellent biocompatibility and non-toxicity of chitosan. Glutaraldehyde was used as cross-linker to covalently bond the AChE, and efficiently prevented leakage of the enzyme from the film. Because of the inherent conductive properties of the MWNT, the immobilized AChE had greater affinity for ATCl and excellent catalytic effect in the hydrolysis of ATCl, with a K(app)(m) value of 132 micromol L(-1), forming thiocholine, which was then oxidized to produce a detectable and rapid response. Under optimum conditions the amperometric current increased linearly with the increasing concentration of ATCl in the range 2.0-400 micromol L(-1), with a detection limit of 0.10 micromol L(-1). Fabrication reproducibility of the sensor was good and the stability was acceptable. The sensor is a promising new tool for characterization of enzyme inhibitors and for pesticide analysis. Abstract.
ESTHER : Du_2007_Anal.Bioanal.Chem_387_1059
PubMedSearch : Du_2007_Anal.Bioanal.Chem_387_1059
PubMedID: 17186224

Title : Molecular characterization of a blood-induced serine carboxypeptidase from the ixodid tick Haemaphysalis longicornis - Motobu_2007_FEBS.J_274_3299
Author(s) : Motobu M , Tsuji N , Miyoshi T , Huang X , Islam MK , Alim MA , Fujisaki K
Ref : Febs J , 274 :3299 , 2007
Abstract : Ticks feed exclusively on blood to obtain their nutrients, but the gene products that mediate digestion processes in ticks remain unknown. We report the molecular characterization and possible function of a serine carboxypeptidase (HlSCP1) identified in the midgut of the hard tick Haemaphysalis longicornis. HlSCP1 consists of 473 amino acids with a peptidase S10 family domain and shows structural similarity with serine carboxypeptidases reported from other arthropods, yeasts, plants and mammals. Endogenous HlSCP1 is strongly expressed in the midgut and is supposed to localize at lysosomal vacuoles and on the surface of epithelial cells. Endogenous HlSCP1, identified as a 53 kDa protein with pI value of 7.5, was detected in the membrane/organelle fraction isolated from the midgut, and its expression was upregulated during the course of blood-feeding. Enzymatic functional assays revealed that a recombinant HlSCP1 (rHlSCP1) expressed in yeast efficiently hydrolyzed the synthetic substrates specific for cathepsin A and thiol protease over a broad range of pH and temperature values. Furthermore, rHlSCP1 was shown to cleave hemoglobin, a major component of the blood-meal. Our results suggest that HlSCP1 may play a vital role in the digestion of the host's blood-meal.
ESTHER : Motobu_2007_FEBS.J_274_3299
PubMedSearch : Motobu_2007_FEBS.J_274_3299
PubMedID: 17542992

Title : Comparison of pesticide sensitivity by electrochemical test based on acetylcholinesterase biosensor - Du_2007_Biosens.Bioelectron_23_285
Author(s) : Du D , Huang X , Cai J , Zhang A
Ref : Biosensors & Bioelectronics , 23 :285 , 2007
Abstract : Based on the change in electrochemical behavior of enzymatic activity induced by pesticide, a novel electrochemical method has been devised for investigation of pesticide sensitivity using acetylcholinesterase (AChE) biosensor. Because of the excellent biocompatibility and good stability of chitosan matrix, it prevented leakage of the AChE from electrode. Multiwall carbon nanotube (MWNT) promoted electron transfer reaction at a lower potential and catalyzed the electro-oxidation of thiocholine, thus amplifying the sensitivity and amperometric response of the biosensor. Four pesticides of carbaryl, malathion, dimethoate and monocrotophos were selected to discuss their inhibition efficiencies to AChE. The inhibition curves were similar to Michealis-Menten and the Michealis-Menten constants (Km) were calculated to be 0.96 microM, 1.78 microM, 1.97 microM and 4.28 microM, respectively. Ninety-five percent reactivation of the inhibited AChE could be regenerated using pralidoxime iodide within 8 min. The proposed electrochemical pesticide sensitivity test exhibited high sensitivity, low cost and simplified procedures, which is a promising new tool for comparison of pesticide sensitivity and for selection of the most efficient enzyme inhibitors.
ESTHER : Du_2007_Biosens.Bioelectron_23_285
PubMedSearch : Du_2007_Biosens.Bioelectron_23_285
PubMedID: 17590326

Title : Evolutionary and biomedical insights from the rhesus macaque genome - Gibbs_2007_Science_316_222
Author(s) : Gibbs RA , Rogers J , Katze MG , Bumgarner R , Weinstock GM , Mardis ER , Remington KA , Strausberg RL , Venter JC , Wilson RK , Batzer MA , Bustamante CD , Eichler EE , Hahn MW , Hardison RC , Makova KD , Miller W , Milosavljevic A , Palermo RE , Siepel A , Sikela JM , Attaway T , Bell S , Bernard KE , Buhay CJ , Chandrabose MN , Dao M , Davis C , Delehaunty KD , Ding Y , Dinh HH , Dugan-Rocha S , Fulton LA , Gabisi RA , Garner TT , Godfrey J , Hawes AC , Hernandez J , Hines S , Holder M , Hume J , Jhangiani SN , Joshi V , Khan ZM , Kirkness EF , Cree A , Fowler RG , Lee S , Lewis LR , Li Z , Liu YS , Moore SM , Muzny D , Nazareth LV , Ngo DN , Okwuonu GO , Pai G , Parker D , Paul HA , Pfannkoch C , Pohl CS , Rogers YH , Ruiz SJ , Sabo A , Santibanez J , Schneider BW , Smith SM , Sodergren E , Svatek AF , Utterback TR , Vattathil S , Warren W , White CS , Chinwalla AT , Feng Y , Halpern AL , Hillier LW , Huang X , Minx P , Nelson JO , Pepin KH , Qin X , Sutton GG , Venter E , Walenz BP , Wallis JW , Worley KC , Yang SP , Jones SM , Marra MA , Rocchi M , Schein JE , Baertsch R , Clarke L , Csuros M , Glasscock J , Harris RA , Havlak P , Jackson AR , Jiang H , Liu Y , Messina DN , Shen Y , Song HX , Wylie T , Zhang L , Birney E , Han K , Konkel MK , Lee J , Smit AF , Ullmer B , Wang H , Xing J , Burhans R , Cheng Z , Karro JE , Ma J , Raney B , She X , Cox MJ , Demuth JP , Dumas LJ , Han SG , Hopkins J , Karimpour-Fard A , Kim YH , Pollack JR , Vinar T , Addo-Quaye C , Degenhardt J , Denby A , Hubisz MJ , Indap A , Kosiol C , Lahn BT , Lawson HA , Marklein A , Nielsen R , Vallender EJ , Clark AG , Ferguson B , Hernandez RD , Hirani K , Kehrer-Sawatzki H , Kolb J , Patil S , Pu LL , Ren Y , Smith DG , Wheeler DA , Schenck I , Ball EV , Chen R , Cooper DN , Giardine B , Hsu F , Kent WJ , Lesk A , Nelson DL , O'Brien W E , Prufer K , Stenson PD , Wallace JC , Ke H , Liu XM , Wang P , Xiang AP , Yang F , Barber GP , Haussler D , Karolchik D , Kern AD , Kuhn RM , Smith KE , Zwieg AS
Ref : Science , 316 :222 , 2007
Abstract : The rhesus macaque (Macaca mulatta) is an abundant primate species that diverged from the ancestors of Homo sapiens about 25 million years ago. Because they are genetically and physiologically similar to humans, rhesus monkeys are the most widely used nonhuman primate in basic and applied biomedical research. We determined the genome sequence of an Indian-origin Macaca mulatta female and compared the data with chimpanzees and humans to reveal the structure of ancestral primate genomes and to identify evidence for positive selection and lineage-specific expansions and contractions of gene families. A comparison of sequences from individual animals was used to investigate their underlying genetic diversity. The complete description of the macaque genome blueprint enhances the utility of this animal model for biomedical research and improves our understanding of the basic biology of the species.
ESTHER : Gibbs_2007_Science_316_222
PubMedSearch : Gibbs_2007_Science_316_222
PubMedID: 17431167
Gene_locus related to this paper: macmu-3neur , macmu-ACHE , macmu-BCHE , macmu-f6rul6 , macmu-f6sz31 , macmu-f6the6 , macmu-f6unj2 , macmu-f6wtx1 , macmu-f6zkq5 , macmu-f7aa58 , macmu-f7ai42 , macmu-f7aim4 , macmu-f7buk8 , macmu-f7cfi8 , macmu-f7cnr2 , macmu-f7cu68 , macmu-f7flv1 , macmu-f7ggk1 , macmu-f7hir7 , macmu-g7n054 , macmu-KANSL3 , macmu-TEX30 , macmu-Y4neur , macmu-g7n4x3 , macmu-i2cy02 , macmu-f7ba84 , macmu-CES2 , macmu-h9er02 , macmu-a0a1d5rbr3 , macmu-a0a1d5q4k5 , macmu-g7mxj6 , macmu-f7dn71 , macmu-f7hkw9 , macmu-f7hm08 , macmu-g7mke4 , macmu-a0a1d5rh04 , macmu-h9fud6 , macmu-f6qwx1 , macmu-f7h4t2 , macmu-h9zaw9 , macmu-f7h550 , macmu-a0a1d5q9w1 , macmu-f7gkb9 , macmu-f7hp78 , macmu-a0a1d5qvu5

Title : Modeling subtype-selective agonists binding with alpha4beta2 and alpha7 nicotinic acetylcholine receptors: effects of local binding and long-range electrostatic interactions - Huang_2006_J.Med.Chem_49_7661
Author(s) : Huang X , Zheng F , Chen X , Crooks PA , Dwoskin LP , Zhan CG
Ref : Journal of Medicinal Chemistry , 49 :7661 , 2006
Abstract : The subtype-selective binding of 14 representative agonists with alpha4beta2 and alpha7 nicotinic acetylcholine receptors (nAChRs) has been studied by performing homology modeling, molecular docking, geometry optimizations, and microscopic and phenomenological binding free energy calculations. All of the computational results demonstrate that the subtype selectivity of the agonists binding with alpha4beta2 and alpha7 7 nAChRs is affected by both local binding and long-range electrostatic interactions between the receptors and the protonated structures of the agonists. The effects of the long-range electrostatic interactions are mainly due to the distinct difference in the net charge of the ligand-binding domain between the two nAChR subtypes. For the alpha4beta2-selective agonists examined, the microscopic binding modes with the alpha4beta2 nAChR are very similar to the corresponding modes with the alpha7 nAChR, and therefore, the subtype selectivity of these agonists binding with alpha4beta2 and alpha7 nAChRs is dominated by the long-range electrostatic interactions. For the alpha7-selective agonists, their microscopic binding modes with the alpha7 nAChR are remarkably different from those with the alpha4beta2 nAChR so that the local binding (including the hydrogen bonding and cation-pi interactions) with the alpha7 nAChR is much stronger than that with the alpha4beta2 nAChR. The calculated phenomenological binding free energies are in good agreement with available experimental data for the relative binding free energies concerning the subtype selectivity of agonists binding with the two different nAChR subtypes. The fundamental insights obtained in the present study should be valuable for future rational design of potential therapeutic agents targeted to specific nAChR subtypes.
ESTHER : Huang_2006_J.Med.Chem_49_7661
PubMedSearch : Huang_2006_J.Med.Chem_49_7661
PubMedID: 17181149

Title : The genome and transcriptomes of the anti-tumor agent Clostridium novyi-NT - Bettegowda_2006_Nat.Biotechnol_24_1573
Author(s) : Bettegowda C , Huang X , Lin J , Cheong I , Kohli M , Szabo SA , Zhang X , Diaz LA, Jr. , Velculescu VE , Parmigiani G , Kinzler KW , Vogelstein B , Zhou S
Ref : Nat Biotechnol , 24 :1573 , 2006
Abstract : Bacteriolytic anti-cancer therapies employ attenuated bacterial strains that selectively proliferate within tumors. Clostridium novyi-NT spores represent one of the most promising of these agents, as they generate potent anti-tumor effects in experimental animals. We have determined the 2.55-Mb genomic sequence of C. novyi-NT, identifying a new type of transposition and 139 genes that do not have homologs in other bacteria. The genomic sequence was used to facilitate the detection of transcripts expressed at various stages of the life cycle of this bacterium in vitro as well as in infections of tumors in vivo. Through this analysis, we found that C. novyi-NT spores contained mRNA and that the spore transcripts were distinct from those in vegetative forms of the bacterium.
ESTHER : Bettegowda_2006_Nat.Biotechnol_24_1573
PubMedSearch : Bettegowda_2006_Nat.Biotechnol_24_1573
PubMedID: 17115055

Title : Novel assay utilizing fluorochrome-tagged physostigmine (Ph-F) to in situ detect active acetylcholinesterase (AChE) induced during apoptosis - Huang_2005_Cell.Cycle_4_140
Author(s) : Huang X , Lee B , Johnson G , Naleway J , Guzikowski A , Dai W , Darzynkiewicz Z
Ref : Cell Cycle , 4 :140 , 2005
Abstract : It was recently reported that acetylcholinesterase (AChE) is expressed in cells undergoing apoptosis and that its presence is essential for assembly of the apoptosome and subsequent caspase-9 activation. To obtain a marker of active AChE that could assay this enzyme in live intact cells and be applicable to fluorescence microscopy and cytometry, the fluorescein-tagged physostigmine (Ph-F), high affinity ligand (inhibitor) reactive with the active center of AChE, was constructed and tested for its ability to in situ label AChE and measure its induction during apoptosis. Ph-F inhibited cholinesterase activity in vitro (IC50 = 10(-6) and 5 x 10(-6) M for equine butyrylcholinesterase and human erythrocyte AChE, respectively) and was a selective marker of cells and structures that were AChE-positive. Thus, exposure of mouse bone marrow cells to Ph-F resulted in the exclusive labeling of megakaryocytes, and of the diaphragm muscle, preferential labeling of the nerve-muscle junctions (end-plates). During apoptosis of carcinoma HeLa cells and leukemic HL-60 or Jurkat cells triggered either by the DNA topoisomerase 1 inhibitor topotecan (TPT) or by oxidative stress (H2O2), the cells become reactive with Ph-F. Their Ph-F derived fluorescence was measured by flow and laser scanning cytometry. The appearance of Ph-F binding sites during apoptosis was preceded by the loss of mitochondrial potential, was concurrent with the presence of activated caspases, and was followed by loss of membrane integrity. At a very early stage of apoptosis, when nucleolar segregation was apparent, the Ph-F binding sites were distinctly localized within the nucleolus and at later stages of apoptosis in the cytoplasm. During apoptosis triggered by TPT, Ph-F binding was preferentially induced in S-phase cells. Our data on megakaryocytes and end-plates indicate that Ph-F reacts with active sites of AChE, and can be used to reveal the presence of this enzyme in live cells and possibly to study its expression in disorders of the neurological cholinergic system. The findings are also compatible with the reports that AChE may be induced during apoptosis. In fact, the simple and rapid Ph-F binding assay may serve as a convenient marker of apoptotic cells. However, the proposed role of active AChE as an essential factor for assembly of the apoptosome and caspase activation is in question because the AChE inhibitors Ph, Ph-F and BW284c51 did not protect the cells from apoptosis induced by TPT or H2O2. Further studies are thus needed to ascertain the induction and role of AChE in apoptosis.
ESTHER : Huang_2005_Cell.Cycle_4_140
PubMedSearch : Huang_2005_Cell.Cycle_4_140
PubMedID: 15611638

Title : Modeling multiple species of nicotine and deschloroepibatidine interacting with alpha4beta2 nicotinic acetylcholine receptor: from microscopic binding to phenomenological binding affinity - Huang_2005_J.Am.Chem.Soc_127_14401
Author(s) : Huang X , Zheng F , Crooks PA , Dwoskin LP , Zhan CG
Ref : Journal of the American Chemical Society , 127 :14401 , 2005
Abstract : A variety of molecular modeling, molecular docking, and first-principles electronic structure calculations were performed to study how the alpha4beta2 nicotinic acetylcholine receptor (nAChR) binds with different species of two typical agonists, (S)-(-)-nicotine and (R)-(-)-deschloroepibatidine, each of which is distinguished by different free bases and protonation states. On the basis of these results, predictions were made regarding the corresponding microscopic binding free energies. Hydrogen-bonding and cation-pi interactions between the receptor and the respective ligands were found to be the dominant factors differentiating the binding strengths of different microscopic binding species. The calculated results and analyses demonstrate that, for each agonist, all the species are interchangeable and can quickly achieve a thermodynamic equilibrium in solution and at the nAChR binding site. This allows quantitation of the equilibrium concentration distributions of the free ligand species and the corresponding microscopic ligand-receptor binding species, their pH dependence, and their contributions to the phenomenological binding affinity. The predicted equilibrium concentration distributions, pK(a) values, absolute phenomenological binding affinities, and their pH dependence are all in good agreement with available experimental data, suggesting that the computational strategy from the microscopic binding species and affinities to the phenomenological binding affinity is reliable for studying alpha4beta2 nAChR-ligand binding. This should provide valuable information for future rational design of drugs targeting nAChRs. The general strategy of the "from-microscopic-to-phenomenological" approach for studying interactions of alpha4beta2 nAChRs with (S)-(-)-nicotine and (R)-(-)-deschloroepibatidine may also be useful in studying other types of ligand-protein interactions involving multiple molecular species of a ligand and in associated rational drug design.
ESTHER : Huang_2005_J.Am.Chem.Soc_127_14401
PubMedSearch : Huang_2005_J.Am.Chem.Soc_127_14401
PubMedID: 16218635

Title : Generation and annotation of the DNA sequences of human chromosomes 2 and 4 - Hillier_2005_Nature_434_724
Author(s) : Hillier LW , Graves TA , Fulton RS , Fulton LA , Pepin KH , Minx P , Wagner-McPherson C , Layman D , Wylie K , Sekhon M , Becker MC , Fewell GA , Delehaunty KD , Miner TL , Nash WE , Kremitzki C , Oddy L , Du H , Sun H , Bradshaw-Cordum H , Ali J , Carter J , Cordes M , Harris A , Isak A , Van Brunt A , Nguyen C , Du F , Courtney L , Kalicki J , Ozersky P , Abbott S , Armstrong J , Belter EA , Caruso L , Cedroni M , Cotton M , Davidson T , Desai A , Elliott G , Erb T , Fronick C , Gaige T , Haakenson W , Haglund K , Holmes A , Harkins R , Kim K , Kruchowski SS , Strong CM , Grewal N , Goyea E , Hou S , Levy A , Martinka S , Mead K , McLellan MD , Meyer R , Randall-Maher J , Tomlinson C , Dauphin-Kohlberg S , Kozlowicz-Reilly A , Shah N , Swearengen-Shahid S , Snider J , Strong JT , Thompson J , Yoakum M , Leonard S , Pearman C , Trani L , Radionenko M , Waligorski JE , Wang C , Rock SM , Tin-Wollam AM , Maupin R , Latreille P , Wendl MC , Yang SP , Pohl C , Wallis JW , Spieth J , Bieri TA , Berkowicz N , Nelson JO , Osborne J , Ding L , Sabo A , Shotland Y , Sinha P , Wohldmann PE , Cook LL , Hickenbotham MT , Eldred J , Williams D , Jones TA , She X , Ciccarelli FD , Izaurralde E , Taylor J , Schmutz J , Myers RM , Cox DR , Huang X , McPherson JD , Mardis ER , Clifton SW , Warren WC , Chinwalla AT , Eddy SR , Marra MA , Ovcharenko I , Furey TS , Miller W , Eichler EE , Bork P , Suyama M , Torrents D , Waterston RH , Wilson RK
Ref : Nature , 434 :724 , 2005
Abstract : Human chromosome 2 is unique to the human lineage in being the product of a head-to-head fusion of two intermediate-sized ancestral chromosomes. Chromosome 4 has received attention primarily related to the search for the Huntington's disease gene, but also for genes associated with Wolf-Hirschhorn syndrome, polycystic kidney disease and a form of muscular dystrophy. Here we present approximately 237 million base pairs of sequence for chromosome 2, and 186 million base pairs for chromosome 4, representing more than 99.6% of their euchromatic sequences. Our initial analyses have identified 1,346 protein-coding genes and 1,239 pseudogenes on chromosome 2, and 796 protein-coding genes and 778 pseudogenes on chromosome 4. Extensive analyses confirm the underlying construction of the sequence, and expand our understanding of the structure and evolution of mammalian chromosomes, including gene deserts, segmental duplications and highly variant regions.
ESTHER : Hillier_2005_Nature_434_724
PubMedSearch : Hillier_2005_Nature_434_724
PubMedID: 15815621
Gene_locus related to this paper: human-ABHD1 , human-LDAH , human-ABHD18 , human-KANSL3 , human-PGAP1 , human-PREPL

Title : The Genomes of Oryza sativa: a history of duplications - Yu_2005_PLoS.Biol_3_e38
Author(s) : Yu J , Wang J , Lin W , Li S , Li H , Zhou J , Ni P , Dong W , Hu S , Zeng C , Zhang J , Zhang Y , Li R , Xu Z , Li X , Zheng H , Cong L , Lin L , Yin J , Geng J , Li G , Shi J , Liu J , Lv H , Li J , Deng Y , Ran L , Shi X , Wang X , Wu Q , Li C , Ren X , Li D , Liu D , Zhang X , Ji Z , Zhao W , Sun Y , Zhang Z , Bao J , Han Y , Dong L , Ji J , Chen P , Wu S , Xiao Y , Bu D , Tan J , Yang L , Ye C , Xu J , Zhou Y , Yu Y , Zhang B , Zhuang S , Wei H , Liu B , Lei M , Yu H , Li Y , Xu H , Wei S , He X , Fang L , Huang X , Su Z , Tong W , Tong Z , Ye J , Wang L , Lei T , Chen C , Chen H , Huang H , Zhang F , Li N , Zhao C , Huang Y , Li L , Xi Y , Qi Q , Li W , Hu W , Tian X , Jiao Y , Liang X , Jin J , Gao L , Zheng W , Hao B , Liu S , Wang W , Yuan L , Cao M , McDermott J , Samudrala R , Wong GK , Yang H
Ref : PLoS Biol , 3 :e38 , 2005
Abstract : We report improved whole-genome shotgun sequences for the genomes of indica and japonica rice, both with multimegabase contiguity, or almost 1,000-fold improvement over the drafts of 2002. Tested against a nonredundant collection of 19,079 full-length cDNAs, 97.7% of the genes are aligned, without fragmentation, to the mapped super-scaffolds of one or the other genome. We introduce a gene identification procedure for plants that does not rely on similarity to known genes to remove erroneous predictions resulting from transposable elements. Using the available EST data to adjust for residual errors in the predictions, the estimated gene count is at least 38,000-40,000. Only 2%-3% of the genes are unique to any one subspecies, comparable to the amount of sequence that might still be missing. Despite this lack of variation in gene content, there is enormous variation in the intergenic regions. At least a quarter of the two sequences could not be aligned, and where they could be aligned, single nucleotide polymorphism (SNP) rates varied from as little as 3.0 SNP/kb in the coding regions to 27.6 SNP/kb in the transposable elements. A more inclusive new approach for analyzing duplication history is introduced here. It reveals an ancient whole-genome duplication, a recent segmental duplication on Chromosomes 11 and 12, and massive ongoing individual gene duplications. We find 18 distinct pairs of duplicated segments that cover 65.7% of the genome; 17 of these pairs date back to a common time before the divergence of the grasses. More important, ongoing individual gene duplications provide a never-ending source of raw material for gene genesis and are major contributors to the differences between members of the grass family.
ESTHER : Yu_2005_PLoS.Biol_3_e38
PubMedSearch : Yu_2005_PLoS.Biol_3_e38
PubMedID: 15685292
Gene_locus related to this paper: orysa-Q7XTC5 , orysa-Q852M6 , orysa-Q8GSE8 , orysa-Q9S7P1 , orysa-Q9FYP7 , orysa-Q5ZBH3 , orysa-Q5ZA26 , orysa-Q5JLP6 , orysa-Q8H5P9 , orysa-Q8H5P5 , orysa-Q7F1Y5 , orysa-Q949C9 , orysa-cbp1 , orysa-cbp3 , orysa-cbpx , orysa-Q33B71 , orysa-Q8GSJ3 , orysa-LPL1 , orysa-Q6YSZ8 , orysa-Q8S5X5 , orysa-Q8LIG3 , orysa-Q6K7F5 , orysa-Q7F1B1 , orysa-Q8H4S9 , orysa-Q69UB1 , orysa-Q9FW17 , orysa-Q337C3 , orysa-Q7F959 , orysa-Q84QZ6 , orysa-Q84QY7 , orysa-Q851E3 , orysa-Q6YTH5 , orysa-Q0JK71 , orysa-Q8S1D9 , orysa-Q5N8V4 , orysa-Q0JCY4 , orysa-Q8GTK2 , orysa-B9EWJ8 , orysa-Q8H3K6 , orysa-Q6ZDG8 , orysa-Q6ZDG6 , orysa-Q6ZDG5 , orysa-Q6ZDG4 , orysa-Q5NAI4 , orysa-Q658B2 , orysa-Q5JMQ8 , orysa-Q5QMD9 , orysa-Q5N7L1 , orysa-Q8RYV9 , orysa-Q8H3R3 , orysa-Q5SNH3 , orysa-Q8W0F0 , orysa-pir7a , orysa-pir7b , orysa-q2qlm4 , orysa-q2qm78 , orysa-q2qm82 , orysa-q2qn31 , orysa-q2qnj4 , orysa-q2qnt9 , orysa-q2qur1 , orysa-q2qx94 , orysa-q2qyi1 , orysa-q2qyj1 , orysa-q2r051 , orysa-q2r077 , orysa-q2ram0 , orysa-q2rat1 , orysa-q2rbb3 , orysa-Q4VWY7 , orysa-q5na00 , orysa-q5nbu1 , orysa-Q5QLC0 , orysa-q5smv5 , orysa-Q5VP27 , orysa-q5vrt2 , orysa-q5w6c5 , orysa-q5z5a3 , orysa-q5z9i2 , orysa-q5z417 , orysa-q5z901 , orysa-Q5ZAM8 , orysa-Q5ZBI5 , orysa-Q5ZCR3 , orysa-q6atz0 , orysa-q6ave2 , orysa-q6f358 , orysa-q6h6s1 , orysa-q6h7i6 , orysa-q6i5q3 , orysa-q6i5u7 , orysa-q6j657 , orysa-q6k3d9 , orysa-q6k4q2 , orysa-q6k880 , orysa-q6l5b6 , orysa-Q6L5F5 , orysa-q6l556 , orysj-q6yse8 , orysa-q6yy42 , orysa-q6yzk1 , orysa-q6z8b1 , orysa-q6z995 , orysa-q6zc62 , orysa-q6zia4 , orysa-q6zjq6 , orysa-q7x7y5 , orysa-Q7XC50 , orysa-q7xej4 , orysa-q7xem8 , orysa-q7xkj9 , orysa-q7xr62 , orysa-q7xr63 , orysa-q7xr64 , orysa-q7xsg1 , orysa-q7xsq2 , orysa-q7xts6 , orysa-q7xv53 , orysa-Q7XVB5 , orysa-Q8L562 , orysa-Q8LQS5 , orysa-Q8RZ40 , orysa-Q8RZ79 , orysa-Q8S0U8 , orysa-Q8S0V0 , orysa-Q8S125 , orysa-Q8SAY7 , orysa-Q8SAY9 , orysa-Q8W3C6 , orysa-Q8W3F2 , orysa-Q8W3F4 , orysa-Q8W3F6 , orysa-Q9LHX5 , orysa-q33aq0 , orysa-q53lh1 , orysa-q53m20 , orysa-q53nd8 , orysa-q60e79 , orysa-q60ew8 , orysa-q67iz2 , orysa-q67iz3 , orysa-q67iz7 , orysa-q67iz8 , orysa-q67j02 , orysa-q67j05 , orysa-q67j07 , orysa-q67j09 , orysa-q67j10 , orysa-q67tr6 , orysa-q67tv0 , orysa-q67uz1 , orysa-q67v34 , orysa-q67wz5 , orysa-q69j38 , orysa-q69k08 , orysa-q69md7 , orysa-q69me0 , orysa-q69pf3 , orysa-q69ti3 , orysa-q69xr2 , orysa-q69y12 , orysa-q69y21 , orysa-q75hy2 , orysa-q75i01 , orysa-Q94JD7 , orysa-Q0J0A4 , orysa-q651a8 , orysa-q651z3 , orysa-q652g4 , orysa-q688m0 , orysa-q688m8 , orysa-q688m9 , orysa-Q6H8G1 , orysi-a2wn01 , orysi-a2xc83 , orysi-a2yh83 , orysi-a2z179 , orysi-a2zef2 , orysi-b8a7e6 , orysi-b8a7e7 , orysi-b8bfe5 , orysi-b8bhp9 , orysj-a3b9l8 , orysj-b9eub8 , orysj-b9eya5 , orysj-b9fi05 , orysj-b9fkb0 , orysj-b9fn42 , orysj-b9gbb7 , orysj-cgep , orysj-PLA7 , orysj-q0d4u5 , orysj-q0djj0 , orysj-q0jaf0 , orysj-q5jl22 , orysj-q5jlw7 , orysj-q5z419 , orysj-q6h7q9 , orysj-q6yvk6 , orysj-q6z6i1 , orysj-q7f8x1 , orysj-q7xcx3 , orysj-q9fwm6 , orysj-q10j20 , orysj-q10ss2 , orysj-q69uw6 , orysj-q94d71 , orysj-q338c0 , orysi-b8bly4 , orysj-b9gbs4 , orysi-a2zb88 , orysj-b9gbs1 , orysi-b8b698 , orysj-pla4 , orysj-pla1

Title : Identification and characterization of pltZ, a gene involved in the repression of pyoluteorin biosynthesis in Pseudomonas sp. M18 - Huang_2004_FEMS.Microbiol.Lett_232_197
Author(s) : Huang X , Zhu D , Ge Y , Hu H , Zhang X , Xu Y
Ref : FEMS Microbiology Letters , 232 :197 , 2004
Abstract : A new regulator gene named pltZ, which is located downstream of the plt gene cluster in the genome of Pseudomonas sp. M18, was identified, sequenced and characterized in this report. The deduced amino acid sequence of PltZ shares significant homology with other bacterial regulators in the TetR family. The chromosomal pltZ disruption mutant gave rise to 4.4-fold enhancement of pyoluteorin biosynthesis but did not exert significant influence on the accumulation of phenazine-1-carboxylic acid compared with the wild-type M18. The negative regulation of pltZ on pyoluteorin biosynthesis was further confirmed by multiplied pltZ gene dosage experiments and pltA'-'lacZ translational fusion analyses.
ESTHER : Huang_2004_FEMS.Microbiol.Lett_232_197
PubMedSearch : Huang_2004_FEMS.Microbiol.Lett_232_197
PubMedID: 15033239
Gene_locus related to this paper: 9psed-q6tlj4

Title : Organizational and mutational analysis of a complete FR-008\/candicidin gene cluster encoding a structurally related polyene complex - Chen_2003_Chem.Biol_10_1065
Author(s) : Chen S , Huang X , Zhou X , Bai L , He J , Jeong KJ , Lee SY , Deng Z
Ref : Chemical Biology , 10 :1065 , 2003
Abstract : The complete gene cluster for biosynthesis of a polyene complex, FR-008, spans 137.2 kb of the genome of Streptomyces sp. FR-008 consisting of six genes for a modular PKS and 15 additional genes. The extensive similarity to the partially characterized candicidin gene cluster in Streptomyces griseus IMRU3570, especially for genes involved in mycosamine biosynthesis, prompted us to compare the compounds produced by Streptomyces sp. FR-008 and Streptomyces griseus IMRU3570, and we found that FR-008 and candicidin complex are identical. A model for biosynthesis of a set of four structurally related FR-008/candicidin compounds was proposed. Deletion of the putative regulatory genes abolished antibiotic production, while disruption of putative glycosyltransferase and GDP-ketosugar aminotransferase functionalities led to the productions of a set of nonmycosaminated aglycones and a novel polyene complex with attachment of altered sugar moiety, respectively.
ESTHER : Chen_2003_Chem.Biol_10_1065
PubMedSearch : Chen_2003_Chem.Biol_10_1065
PubMedID: 14652074
Gene_locus related to this paper: 9acto-q6w5p8 , strgr-pabt

Title : Metal chelation as a potential therapy for Alzheimer's disease - Cuajungco_2000_Ann.N.Y.Acad.Sci_920_292
Author(s) : Cuajungco MP , Faget KY , Huang X , Tanzi RE , Bush AI
Ref : Annals of the New York Academy of Sciences , 920 :292 , 2000
Abstract : Alzheimer's disease is a rapidly worsening public health problem. The current lack of effective treatments for Alzheimer's disease makes it imperative to find new pharmacotherapies. At present, the treatment of symptoms includes use of acetylcholinesterase inhibitors, which enhance acetylcholine levels and improve cognitive functioning. Current reports provide evidence that the pathogenesis of Alzheimer's disease is linked to the characteristic neocortical amyloid-beta deposition, which may be mediated by abnormal metal interaction with A beta as well as metal-mediated oxidative stress. In light of these observations, we have considered the development of drugs that target abnormal metal accumulation and its adverse consequences, as well as prevention or reversal of amyloid-beta plaque formation. This paper reviews recent observations on the possible etiologic role of A beta deposition, its redox activity, and its interaction with transition metals that are enriched in the neocortex. We discuss the effects of metal chelators on these processes, list existing drugs with chelating properties, and explore the promise of this approach as a basis for medicinal chemistry in the development of novel Alzheimer's disease therapeutics. therapeutics
ESTHER : Cuajungco_2000_Ann.N.Y.Acad.Sci_920_292
PubMedSearch : Cuajungco_2000_Ann.N.Y.Acad.Sci_920_292
PubMedID: 11193167

Title : Identification of target promoters for the Bacillus subtilis extracytoplasmic function sigma factor, sigma W - Huang_1999_Mol.Microbiol_31_361
Author(s) : Huang X , Gaballa A , Cao M , Helmann JD
Ref : Molecular Microbiology , 31 :361 , 1999
Abstract : The Bacillus subtilis sigW gene encodes an extracytoplasmic function (ECF) sigma factor that is expressed in early stationary phase from a sigW-dependent autoregulatory promoter, PW. Using a consensus-based search procedure, we have identified 15 operons preceded by promoters similar in sequence to PW. At least 14 of these promoters are dependent on sigma W both in vivo and in vitro as judged by lacZ reporter fusions, run-off transcription assays and nucleotide resolution start site mapping. We conclude that sigma W controls a regulon of more than 30 genes, many of which encode membrane proteins of unknown function. The sigma W regulon includes a penicillin binding protein (PBP4*) and a co-transcribed amino acid racemase (RacX), homologues of signal peptide peptidase (YteI), flotillin (YuaG), ABC transporters (YknXYZ), non-haem bromoperoxidase (YdjP), epoxide hydrolase (YfhM) and three small peptides with structural similarities to bacteriocin precursor polypeptides. We suggest that sigma W activates a large stationary-phase regulon that functions in detoxification, production of anti-microbial compounds or both.
ESTHER : Huang_1999_Mol.Microbiol_31_361
PubMedSearch : Huang_1999_Mol.Microbiol_31_361
PubMedID: 9987136
Gene_locus related to this paper: bacsu-ydjp