Huang H

References (75)

Title : Facile and selective recognition of sulfonylurea pesticides based on the multienzyme-like activities enhancement of nanozymes combining sensor array - Tian_2024_J.Hazard.Mater_469_133847
Author(s) : Tian T , Song D , Zhang L , Huang H , Li Y
Ref : J Hazard Mater , 469 :133847 , 2024
Abstract : Traditional identification methods based on cholinesterase inhibition are limited to recognizing organic phosphorus and carbamate esters, and their response to sulfonylurea pesticides is weak. Residual sulfonylurea pesticides can pose a threat to human health. So, it is very important to develop an effective, rapid and portable method for sulfonylurea pesticides detection. Herein, we first found that sulfonylurea pesticides have activity-enhancing effects on copper-based nanozymes, and then combined them with the array technology to construct a six-channel sensing array method for selectively identifying sulfonylurea pesticides and detecting total concentration of sulfonylurea pesticides (the limit of detection was 0.03 microg/mL). This method has good selectivity towards sulfonylurea pesticides. In addition, a smartphone-based colorimetric paper sensor analysis method was developed to achieve the on-site detection of the total concentration of sulfonylurea pesticides. And this array can also be used for individual differentiation (1-100 microg/mL). Our work not only investigates the specific responses of copper-based nanozymes to sulfonylurea pesticides, but also develops a simple method that contributes to directly detect sulfonylurea pesticides at the source of pollution, providing insights for further research on sulfonylurea pesticides detection and filling the gap in pesticide residue studies.
ESTHER : Tian_2024_J.Hazard.Mater_469_133847
PubMedSearch : Tian_2024_J.Hazard.Mater_469_133847
PubMedID: 38422731

Title : Corner Engineering: Tailoring Enzymes for Enhanced Resistance and Thermostability in Deep Eutectic Solvents - Wang_2023_Angew.Chem.Int.Ed.Engl__e202315125
Author(s) : Wang X , Sheng Y , Cui H , Qiao J , Song Y , Li X , Huang H
Ref : Angew Chem Int Ed Engl , :e202315125 , 2023
Abstract : Deep eutectic solvents (DESs), heralded for their synthesis simplicity, economic viability, and reduced volatility and flammability, have found increasing application in biocatalysis. However, challenges persist due to a frequent diminution in enzyme activity and stability. Herein, we developed a general protein engineering strategy, termed corner engineering, to acquire DES-resistant and thermostable enzymes via precisely tailoring of the transition region in enzyme structure. Employing Bacillus subtilis lipase A (BSLA) as a model, we delineated the engineering process, yielding five multi-DESs resistant variants with highly improved thermostability, such as K889E/N89K exhibited up to a 10.0-fold catalytic efficiency (kcat/KM) increase in 30% (v/v) ChCl:acetamide and 4.1-fold in 95% (v/v) ChCl:ethylene glycol accompanying 6.7-fold thermal resistance improvement than wild type at ~50 degreesC. The generality of the optimized approach was validated by two extra industrial enzymes, endo-beta-1,4-glucanase PvCel5A (used for biofuel production) and esterase Bs2Est (plastics degradation). The molecular investigations revealed that increased water molecules at substrate binding sites and finetuned helix formation at the corner region are two dominant determinants governing elevated resistance and thermostability. This study, coupling corner engineering with obtained molecular insights, illuminates enzyme-DES interaction patterns and fosters the rational design of more DES-resistant and thermostable enzymes in biocatalysis and biotransformation.
ESTHER : Wang_2023_Angew.Chem.Int.Ed.Engl__e202315125
PubMedSearch : Wang_2023_Angew.Chem.Int.Ed.Engl__e202315125
PubMedID: 38010210
Gene_locus related to this paper: bacsu-lip , bacsu-pnbae

Title : Discovery and mechanism-guided engineering of BHET hydrolases for improved PET recycling and upcycling - Li_2023_Nat.Commun_14_4169
Author(s) : Li A , Sheng Y , Cui H , Wang M , Wu L , Song Y , Yang R , Li X , Huang H
Ref : Nat Commun , 14 :4169 , 2023
Abstract : Although considerable research achievements have been made to address the plastic crisis using enzymes, their applications are limited due to incomplete degradation and low efficiency. Herein, we report the identification and subsequent engineering of BHETases, which have the potential to improve the efficiency of PET recycling and upcycling. Two BHETases (ChryBHETase and BsEst) are identified from the environment via enzyme mining. Subsequently, mechanism-guided barrier engineering is employed to yield two robust and thermostable deltaBHETases with up to 3.5-fold enhanced k(cat)/K(M) than wild-type, followed by atomic resolution understanding. Coupling deltaBHETase into a two-enzyme system overcomes the challenge of heterogeneous product formation and results in up to 7.0-fold improved TPA production than seven state-of-the-art PET hydrolases, under the conditions used here. Finally, we employ a deltaBHETase-joined tandem chemical-enzymatic approach to valorize 21 commercial post-consumed plastics into virgin PET and an example chemical (p-phthaloyl chloride) for achieving the closed-loop PET recycling and open-loop PET upcycling.
ESTHER : Li_2023_Nat.Commun_14_4169
PubMedSearch : Li_2023_Nat.Commun_14_4169
PubMedID: 37443360
Gene_locus related to this paper: 9flao-ChryBHETase , bacsu-pnbae

Title : Smartphone-assisted sensor array constructed by copper-based laccase-like nanozymes for specific identification and discrimination of organophosphorus pesticides - Song_2023_Food.Chem_424_136477
Author(s) : Song D , Tian T , Yang X , Wang L , Sun Y , Li Y , Huang H
Ref : Food Chem , 424 :136477 , 2023
Abstract : Accurate pesticide identification is of great importance for regulating food safety. However, the discrimination between organophosphorus pesticides (OPs) and carbamate pesticides (CPs) is still a challenge for existing analytical methods based on cholinesterase inhibition. It mainly because of the similar inhibitory effect of OPs and CPs on cholinesterase. Herein, we found that OPs and CPs differentially affected nanozymes with laccase-like activity, which would be interfered by OPs in different degrees rather than CPs. Thus, we fabricated a nanozyme sensor array and successfully achieved the OPs identification and similar individual discrimination, ignoring the interference from CPs or other potential interferents (antibiotics, ions, other pesticides). On the basis of nanozyme sensor array, a portable method using smartphone was constructed and utilized to determine OPs in fruits and vegetables. This work would contribute to the development of portable sensors and the highly selective identification and discrimination of OPs in complex samples.
ESTHER : Song_2023_Food.Chem_424_136477
PubMedSearch : Song_2023_Food.Chem_424_136477
PubMedID: 37263094

Title : Identification of pancreatic lipase inhibitors from Eucommia ulmoides tea by affinity-ultrafiltration combined UPLC-Orbitrap MS and in vitro validation - Huang_2023_Food.Chem_426_136630
Author(s) : Huang H , Han MH , Gu Q , Wang JD , Zhao H , Zhai BW , Nie SM , Liu ZG , Fu YJ
Ref : Food Chem , 426 :136630 , 2023
Abstract : Pancreatic lipase inhibitors can reduce blood lipids by inactivating the catalytic activity of human pancreatic lipase, a key enzyme involved in triglyceride hydrolysis, which helps control some dyslipidemic diseases. The ability of Eucommia ulmoides tea to improve fat-related diseases is closely related to the natural inhibitory components of pancreatic lipase contained in the tea. In this study, fifteen pancreatic lipase inhibitors were screened and identified from Eucommia ulmoides tea by affinity-ultrafiltration combined UPLC-Q-Exactive Orbitrap/MS. Four representative components of geniposidic acid, quercetin-3-O-sambuboside, isochlorogenic acid A, and quercetin with high binding degrees were further verified by nanoscale differential scanning fluorimetry (nanoDSF) and enzyme inhibitory assays. The results of flow cytometry showed that they could significantly reduce the activity of pancreatic lipase in AR42J cells induced by palmitic acid in a concentration-dependent manner. Our findings suggest that Eucommia ulmoides tea may be a promising resource for pancreatic lipase inhibitors of natural origin.
ESTHER : Huang_2023_Food.Chem_426_136630
PubMedSearch : Huang_2023_Food.Chem_426_136630
PubMedID: 37352710

Title : Optimal dose of neostigmine antagonizing cisatracurium-induced shallow neuromuscular block in elderly patients: a randomized control study - Cao_2023_BMC.Anesthesiol_23_269
Author(s) : Cao M , Huang H , Tong J , Ou Y , Liao Y
Ref : BMC Anesthesiol , 23 :269 , 2023
Abstract : BACKGROUND: Residual neuromuscular block after using neuromuscular blocking agents is a common and potentially harmful complication of general anesthesia. Neostigmine is a widely used antagonist, but its optimal dose for elderly patients is unclear. OBJECTIVES: To compare the optimal dosage and safety of neostigmine for reversing shallow residual block in elderly patients after cisatracurium-induced neuromuscular block. METHODS: A randomized controlled trial was conducted in 196 elderly patients undergoing non-cardiac surgery under general anesthesia with cisatracurium. Patients were assigned to receive either no neostigmine (control group) or neostigmine at 20 microg/kg, 40 microg/kg or 50 microg/kg when train-of-four (TOF) ratio reached 0.2 at the end of surgery. The primary outcome was the time to reach TOF ratio of 0.9 after administration. Secondary outcomes included TOF ratio at 10 min after administration, postoperative nausea and vomiting, postoperative cognitive impairment and post-anesthesia care unit (PACU) stay time. RESULTS: The time to reach TOF ratio of 0.9 in the 20 microg/kg, 40 microg/kg and 50 microg/kg groups was significantly shorter than the control group (H = 104.257, P < 0.01), and the time of 40 microg/kg group and 50 microg/kg group was significantly shorter than the 20 microg/kg group (P < 0.001). There was no significant difference between 40 microg/kg and 50 microg/kg groups (P = 0.249). The TOF ratio at 10 min after administration showed similar results. There were no significant differences among groups in postoperative nausea and vomiting, postoperative cognitive impairment or post-operation hospital stay. CONCLUSIONS: Timely use of neostigmine after general anesthesia in elderly patients can significantly shorten time of TOF value reaching 0.9, among which 40 microg/kg dosage may be a more optimized choice. TRIAL REGISTRATION: this study was registered on (ChiCTR2100054685, 24/12/2021).
ESTHER : Cao_2023_BMC.Anesthesiol_23_269
PubMedSearch : Cao_2023_BMC.Anesthesiol_23_269
PubMedID: 37563623

Title : Rational redesign of thermophilic PET hydrolase LCCICCG to enhance hydrolysis of high crystallinity polyethylene terephthalates - Ding_2023_J.Hazard.Mater_453_131386
Author(s) : Ding Z , Xu G , Miao R , Wu N , Zhang W , Yao B , Guan F , Huang H , Tian J
Ref : J Hazard Mater , 453 :131386 , 2023
Abstract : Polyethylene terephthalate (PET)-degrading enzymes represent a promising solution to the plastic pollution. However, PET-degrading enzymes, even thermophilic PETase, can effectively degrade low-crystallinity (-8%) PETs, but exhibit weak depolymerization of more common, high-crystallinity (30-50%) PETs. Here, based on the thermophilic PETase, LCCICCG, we proposed two strategies for rational redesign of LCCICCG using the machine learning tool, Preoptem, combined with evolutionary analysis. Six single-point mutants (S32L, D18T, S98R, T157P, E173Q, N213P) were obtained that exhibit higher catalytic efficiency towards PET powder than wild-type LCCICCG at 75 degreesC. Additionally, the optimal temperature for degrading 39.07% crystalline PET increased from 65 degreesC in the wild-type LCCICCG to between 75 and 80 degreesC in the LCCICCG_I6M mutant that carries all six single-point mutations. Especially, the LCCICCG_I6M mutant has a significantly higher degradation effect on some commonly used bottle-grade plastic powders at 75-80 degreesC than that of wild type. The enzymatic digestion of ground 31.30% crystalline PET water bottles by LCCICCG_I6M yielded 31.91 +/- 0.99 mM soluble products in 24 h, which was 3.64 times that of LCCICCG (8.77 +/- 1.52 mM). Overall, this study provides a feasible route for engineering thermostable enzymes that can degrade high-crystallinity PET plastic.
ESTHER : Ding_2023_J.Hazard.Mater_453_131386
PubMedSearch : Ding_2023_J.Hazard.Mater_453_131386
PubMedID: 37043849
Gene_locus related to this paper: 9bact-g9by57

Title : Characterization of deglycosylated metabolites of platycosides reveals their biotransformation after oral administration - Yau_2022_Food.Chem_393_133383
Author(s) : Yau LF , Huang H , Tong TT , Bai LB , Zhu GY , Hou Y , Bai G , Jiang ZH
Ref : Food Chem , 393 :133383 , 2022
Abstract : Platycodon grandiflorus is a well-known edible and medicinal plant that has been developed for dietary supplements or functional foods to relieve pulmonary disorders. Platycosides are the main active constituents of P. grandiflorus with multiple pharmacological activities. However, their metabolic fates after dietary consumption are still unclear. Herein, 25 deglycosylated metabolites of platycosides were identified, most of which were identified in vivo for the first time. Notably, 3-O-beta-d-glucopyranosyl platycosides could be absorbed into the bloodstream, and their structures were unambiguously characterized with the aid of chemically prepared standards, including two new compounds (M3 and M11). These findings reveal that both intestinal bacterial metabolism and hydrolysis of ester linkage at C-28 by carboxylesterases in liver are the possible in vivo deglycosylation metabolism pathway of platycosides. This study greatly facilitated our understanding of the fate of the platycosides after dietary consumption of P. grandiflorus products.
ESTHER : Yau_2022_Food.Chem_393_133383
PubMedSearch : Yau_2022_Food.Chem_393_133383
PubMedID: 35671663

Title : Antinociceptive Effects and Interaction Mechanisms of Intrathecal Pentazocine and Neostigmine in Two Different Pain Models in Rats - Huang_2022_Pain.Res.Manag_2022_4819910
Author(s) : Huang H , Bai X , Zhang K , Guo J , Wu S , Ouyang H
Ref : Pain Res Manag , 2022 :4819910 , 2022
Abstract : BACKGROUND: Pentazocine produces a wide variety of actions in the treatment of perioperative analgesia. Neostigmine is a cholinesterase inhibitor used to antagonize the residual effects of muscle relaxants and also produces an analgesic effect. OBJECTIVES: To investigate the analgesic effects of intrathecally injected pentazocine and neostigmine and their interaction. METHODS: Sprague-Dawley rats were used to test the analgesic effect of pentazocine and neostigmine using the paw formalin pain model and the incision mechanical allodynia model. Pentazocine (3, 10, 30, and 100 microg), neostigmine (0.3, 1, 3, and 10 microg) or a pentazocine-neostigmine mixture were separately injected to evaluate their antinociceptive effects alone on the treatment groups. The corresponding control group received an intrathecal injection containing the same volume of saline. The formalin pain test, or the plantar incision pain behavior test were performed 30 minutes later. Isobolographic analysis was used to evaluate the interaction between pentazocine and neostigmine. Intrathecally administered selective mu-opioid receptor antagonist CTAP, selective kappa-opioid receptor antagonist nor-Binaltorphimine (nor-BNI), nonselective opioid receptor antagonist naloxone, and muscarinic acetylcholine receptor antagonist atropine were also used to test the possible interaction mechanism. These antagonists were used 30 minutes before the pentazocine and neostigmine mixtures which were intrathecally injected. RESULTS: Intrathecally administered pentazocine (3, 10, 30, and 100 microg) and neostigmine (0.3, 1, 3, and 10 microg) alone had a marked dose-related impact on suppressing the biphasic responses in the formalin test. Pentazocine (3, 10, 30, and 100 microg) and neostigmine (0.3, 1, 3, and 10 microg) alone attenuated the mechanical allodynia in a plantar incision model in a dose-dependent manner. Isobolographic analysis revealed that the mixture of intrathecal pentazocine and neostigmine synergistically decreased both phase I and II activity in the formalin test and mechanical allodynia in the plantar incision model. Pretreatment of intrathecally administered nor-BNI, naloxone, atropine, but not CTAP, antagonized the analgesic effect of the pentazocine-neostigmine mixture. CONCLUSIONS: All of these results suggest that the combined application of pentazocine and neostigmine is an effective way to relieve pain from formalin and acute incision mechanical allodynia. The synergistic effect between pentazocine and neostigmine is mostly attributed to the kappa-opioid receptor and the cholinergic receptor in the spinal cord.
ESTHER : Huang_2022_Pain.Res.Manag_2022_4819910
PubMedSearch : Huang_2022_Pain.Res.Manag_2022_4819910
PubMedID: 35646201

Title : Learning and memory impairment induced by 1,4-butanediol is regulated by ERK1\/2-CREB-BDNF signaling pathways in PC12 cells - Chen_2022_Metab.Brain.Dis__
Author(s) : Chen C , Bu L , Liu H , Rang Y , Huang H , Xiao X , Ou G , Liu C
Ref : Metabolic Brain Disease , : , 2022
Abstract : 1,4-butanediol (1,4-BD) is a known gamma-hydroxybutyric acid (GHB) precursor which affects the nervous system after ingestion, leading to uncontrolled behavioral consequences. In the present study, we investigated whether 1,4-BD induces oxidative stress and inflammation in PC12 cells and evaluated the toxic effects of 1,4-BD associates with learning and memory. CCK-8 results revealed a dose-effect relationship between the cell viability of PC12 cells and 1,4-BD when the duration of action was 2 h or 4 h. Assay kits results showed that 1,4-BD decreased the levels of Glutathione (GSH), Glutathione peroxidase (GSH-px), Superoxide dismutase (SOD), Acetylcholine (Ach) and increased the levels of Malondialdehyde (MDA), Nitric oxide (NO) and Acetylcholinesterase (AchE). Elisa kits results indicated that 1,4-BD decreased the levels of synaptophysin I (SYN-1), Postsynaptic density protein-95 (PSD-95), Growth associated protein-43 (GAP-43) and increased the levels of Tumor necrosis factor alpha (TNF-alpha) and Interleukin- 6 (IL-6). RT-PCR results showed that the mRNA levels of PSD-95, SYN-1 and GAP-43 were significantly decreased. The expression of phosphorylation extracellular signal-regulated protein kinase 1/2 (p-ERK1/2), phosphorylation cAMP response element binding protein (p-CREB) and brain-derived neurotrophic factor (BDNF) proteins were significantly decreased in PC12 cells by protein blotting. Overall, these results suggest that 1,4-BD may affect synaptic plasticity via the ERK1/2-CREB-BDNF pathway, leading to Ach release reduction and ultimately to learning and memory impairment. Furthermore, oxidative stress and inflammation induced by 1,4-BD may also result in learning and memory deficits. These findings will enrich the toxicity data of 1.4-BD associated with learning and memory impairment.
ESTHER : Chen_2022_Metab.Brain.Dis__
PubMedSearch : Chen_2022_Metab.Brain.Dis__
PubMedID: 35348994

Title : Single-atom Ce-N-C nanozyme bioactive paper with a 3D-printed platform for rapid detection of organophosphorus and carbamate pesticide residues - Song_2022_Food.Chem_387_132896
Author(s) : Song G , Zhang J , Huang H , Wang X , He X , Luo Y , Li JC , Huang K , Cheng N
Ref : Food Chem , 387 :132896 , 2022
Abstract : Rapid detection of pesticide residues based on enzyme mimics has recently attracted much interest. However, most nanozymes have low activity. Herein, a "single-atom Ce-N-C nanozyme" (SACe-N-C nanozyme) was rationally devised and verified to mimic peroxidase (POD-like) with superior activity. Based on its high POD-like activities and cascaded catalytic reactions with acetylcholinesterase (AChE), we constructed a bioactive paper for the detection of pesticide residues, which offered a portable approach to monitor fruits and vegetables within 30 min. More importantly, a 3D printed platform was integrated on the basis of SACe-N-C bioactive paper to achieve on-site portable testing of omethoate, methamidophos, carbofuran, and carbosulfan, showing limits of detection (LODs) of 55.83, 71.51, 81.81, and 74.98 ng/mL, respectively. The recovery rates were 84.09-104.68%. This study provided new insight into the design of novel single-atom nanozymes for cascaded catalytic detection and other rapid detection applications with high efficiency and low cost.
ESTHER : Song_2022_Food.Chem_387_132896
PubMedSearch : Song_2022_Food.Chem_387_132896
PubMedID: 35421648

Title : Enzyme catalyzes ester bond synthesis and hydrolysis: The key step for sustainable usage of plastics - Lai_2022_Front.Microbiol_13_1113705
Author(s) : Lai J , Huang H , Lin M , Xu Y , Li X , Sun B
Ref : Front Microbiol , 13 :1113705 , 2022
Abstract : Petro-plastic wastes cause serious environmental contamination that require effective solutions. Developing alternatives to petro-plastics and exploring feasible degrading methods are two solving routes. Bio-plastics like polyhydroxyalkanoates (PHAs), polylactic acid (PLA), polycaprolactone (PCL), poly (butylene succinate) (PBS), poly (ethylene furanoate) s (PEFs) and poly (ethylene succinate) (PES) have emerged as promising alternatives. Meanwhile, biodegradation plays important roles in recycling plastics (e.g., bio-plastics PHAs, PLA, PCL, PBS, PEFs and PES) and petro-plastics poly (ethylene terephthalate) (PET) and plasticizers in plastics (e.g., phthalate esters, PAEs). All these bio- and petro-materials show structure similarity by connecting monomers through ester bond. Thus, this review focused on bio-plastics and summarized the sequences and structures of the microbial enzymes catalyzing ester-bond synthesis. Most of these synthetic enzymes belonged to alpha/beta-hydrolases with conserved serine catalytic active site and catalyzed the polymerization of monomers by forming ester bond. For enzymatic plastic degradation, enzymes about PHAs, PBS, PCL, PEFs, PES and PET were discussed, and most of the enzymes also belonged to the alpha/beta hydrolases with a catalytic active residue serine, and nucleophilically attacked the ester bond of substrate to generate the cleavage of plastic backbone. Enzymes hydrolysis of the representative plasticizer PAEs were divided into three types (I, II, and III). Type I enzymes hydrolyzed only one ester-bond of PAEs, type II enzymes catalyzed the ester-bond of mono-ester phthalates, and type III enzymes hydrolyzed di-ester bonds of PAEs. Divergences of catalytic mechanisms among these enzymes were still unclear. This review provided references for producing bio-plastics, and degrading or recycling of bio- and petro-plastics from an enzymatic point of view.
ESTHER : Lai_2022_Front.Microbiol_13_1113705
PubMedSearch : Lai_2022_Front.Microbiol_13_1113705
PubMedID: 36713200

Title : Cloning and Characterization of Three Novel Enzymes Responsible for the Detoxification of Zearalenone - Zhang_2022_Toxins.(Basel)_14_
Author(s) : Zhang Y , Liu X , Zhang X , Huang H
Ref : Toxins (Basel) , 14 : , 2022
Abstract : Zearalenone is a common mycotoxin contaminant in cereals that causes severe economic losses and serious risks to health of human and animals. Many strategies have been devised to degrade ZEN and keep food safe. The hydrolase ZHD101 from Clonostachys rosea, which catalyzes the hydrolytic degradation of ZEN, has been studied widely. In the current research, three new enzymes that have the capacity to detoxify ZEN were identified, namely CLA, EXO, and TRI, showing 61%, 63%, and 97% amino acids identities with ZHD101, respectively. Three coding genes was expressed as heterologous in Escherichia coli BL21. Through biochemical analysis, the purified recombinant CLA, EXO, TRI, and ZHD101 exhibited high activities of degrading ZEN with the specific activity of 114.8 U/mg, 459.0 U/mg, 239.8 U/mg, and 242.8 U/mg. The optimal temperatures of CLA, EXO, TRI, and ZHD101 were 40 degreesC, 40 degreesC, 40 degreesC, and 45 degreesC, and their optimum pH were 7.0, 9.0, 9.5, and 9.0, respectively. Our study demonstrated that the novel enzymes CLA, EXO, and TRI possessed high ability to degrade ZEN from the model solutions and could be the promising candidates for ZEN detoxification in practical application.
ESTHER : Zhang_2022_Toxins.(Basel)_14_
PubMedSearch : Zhang_2022_Toxins.(Basel)_14_
PubMedID: 35202110

Title : Detection of Carboxylesterase 1 and Chlorpyrifos with ZIF-8 Metal-Organic Frameworks Using a Red Emission BODIPY-Based Probe - Shen_2021_ACS.Appl.Mater.Interfaces__
Author(s) : Shen B , Ma C , Ji Y , Dai J , Li B , Zhang X , Huang H
Ref : ACS Appl Mater Interfaces , : , 2021
Abstract : In this work, a red emission fluorescent probe CBZ-BOD@zeolitic imidazolate framework-8 (ZIF-8) was fabricated based on metal-organic frameworks (MOFs) for detecting carboxylesterase 1 (CES1). The small molecule probe CBZ-BOD was first synthesized and then used to prepare the functionalized MOF material. ZIF-8 was chosen as an encapsulation shell to improve the detection properties of CBZ-BOD. Using this unique porous materials, ultrasensitive quantification of CES1 and chlorpyrifos was successfully realized. The low detection limit and high fluorescence quantum yield were calculated as 1.15 ng/mL and 0.65 for CBZ-BOD@ZIF-8, respectively. CBZ-BOD@ZIF-8 has good biocompatibility and was successfully applied to monitor the activity of CES1 in living cells. A molecular docking study was used to explore the binding of CES1 and CBZ-BOD, finding that CES1 can bind with the probe before and after hydrolysis. This type of materialized probe can inspire the development of fluorescent tools for further exploration of many pathological processes.
ESTHER : Shen_2021_ACS.Appl.Mater.Interfaces__
PubMedSearch : Shen_2021_ACS.Appl.Mater.Interfaces__
PubMedID: 33569946

Title : An efficient phthalate ester-degrading Bacillus subtilis: Degradation kinetics, metabolic pathway, and catalytic mechanism of the key enzyme - Xu_2021_Environ.Pollut_273_116461
Author(s) : Xu Y , Liu X , Zhao J , Huang H , Wu M , Li X , Li W , Sun X , Sun B
Ref : Environ Pollut , 273 :116461 , 2021
Abstract : Phthalate ester pollution in the environment and food chain is frequently reported. Microbial treatment is a green and efficient method for solving this problem. The isolation and systematic investigation of microorganisms generally recognized as safe (GRAS) will provide useful resources. A GRAS Bacillus subtilis strain, BJQ0005, was isolated from Baijiu fermentation starter and efficiently degraded phthalate esters (PAEs). The half-lives for di-isobutyl phthalate, di-butyl phthalate and di-(2-ethylhexyl) phthalate were 3.93, 4.28, and 25.49 h, respectively, from the initial amount of 10 mg per 10 mL reaction mixture, which are records using wild-type strains. Genome sequencing and metabolic intermediate analysis generated the whole metabolic pathway. Eighteen enzymes from the alpha/beta hydrolase family were expressed. Enzymes GTW28_09400 and GTW28_13725 were capable of single ester bond hydrolysis of PAEs, while GTW28_17760 hydrolyzed di-ester bonds of PAEs. Using molecular docking, a possible mechanism affecting enzymatic ester bond hydrolysis of mono-butyl phthalate was proposed of GTW28_17760. The carboxyl group generated by the first hydrolysis step interacted with histidine in the catalytic active center, which negatively affected enzymatic hydrolysis. Isolation and systematic investigation of the PAE degradation characteristics of B. subtilis will promote the green and safe treatment of PAEs in the environment and food industry.
ESTHER : Xu_2021_Environ.Pollut_273_116461
PubMedSearch : Xu_2021_Environ.Pollut_273_116461
PubMedID: 33485001
Gene_locus related to this paper: bacsu-pnbae

Title : The Role of N-myc Downstream-Regulated Gene Family in Glioma Based on Bioinformatics Analysis - Tang_2021_DNA.Cell.Biol_40_949
Author(s) : Tang T , Wang H , Han Y , Huang H , Niu W , Fei M , Zhu Y
Ref : DNA & Cell Biology , 40 :949 , 2021
Abstract : Glioma is the most common type of primary tumor in the central nervous system, and the molecular mechanisms remain elusive. N-myc downstream-regulated gene (NDRG) family is reported to take part in the pathogenesis of various diseases, including some preliminary exploration in glioma. However, there has been no bioinformatics analysis of NDRG family in glioma yet. Herein, we focused on the expression changes of NDRGs with their value in predicting patients' prognoses, upstream regulatory mechanisms (DNA mutation, DNA methylation, transcription factors, and microRNA regulation) and gene enrichment analysis based on co-expressed genes with data from public databases. Furthermore, the expression pattern of NDRGs was verified by the paired glioma and peritumoral samples in our institute. It was suggested that NDRGs were differentially expressed genes in glioma. In particular, the lower expression of NDRG2 or NDRG4 could serve as a predictor of higher grade tumor and poorer prognosis. Also, NDRGs might play a crucial role in signal transduction, energy metabolism, and cross-talk among cells in glioma, under the control of a complex regulatory network. This study enables us to better understand the role of NDRGs in glioma and with further research, it may contribute to the development of glioma treatment.
ESTHER : Tang_2021_DNA.Cell.Biol_40_949
PubMedSearch : Tang_2021_DNA.Cell.Biol_40_949
PubMedID: 34115542

Title : Construction of a red emission fluorescent protein chromophore-based probe for detection of carboxylesterase 1 and carbamate pesticide in culture cells - Dai_2021_Talanta_223_121744
Author(s) : Dai J , Hou Y , Wu J , Zhong G , Gao R , Shen B , Huang H
Ref : Talanta , 223 :121744 , 2021
Abstract : Designing fluorescent probe for detecting carboxylesterase 1 is remains challenging. Herein, a red emission human carboxylesterase 1 (CES1) probe (CAE-FP) was synthesized based on fluorescent protein chromophore. Probe CAE-FP can specific detect human CES1 with high selectively. The fluorescence quantum yield was calucated as 0.19. The carboxylic acid ester in CAE-FP could be easily hydrolyzed by CES1 under physiological conditions, and this process could induce the obvious fluorescence signal in red emission region. The detection limit of CES1 was calculated as 84.5 ng/mL. Due to the biological detoxification mechanism of carboxylesterase and the obvious inhibitory effect of pesticides on its activity, CAE-FP was applied to detect carbamate pesticide and have achieved good application results. Since fluorescent protein chromophore has excellent biocompatibility, probe CAE-FP with good cell membrane permeable and was successfully applied to monitor the real activities of CES1 in living cells. In summary, this is one of the few reported fluorescent probes that can specific detect the real-time activity of CES1 in biological samples. Besides, we first applied the fluorescent protein chromophore to construct the specific target enzyme probe. This work would contribute to further investigate CES1-associated physiological and pathological processe.
ESTHER : Dai_2021_Talanta_223_121744
PubMedSearch : Dai_2021_Talanta_223_121744
PubMedID: 33298268

Title : Deletion of soluble epoxide hydrolase suppressed chronic kidney disease-related vascular calcification by restoring Sirtuin 3 expression - He_2021_Cell.Death.Dis_12_992
Author(s) : He W , Huang J , Liu Y , Xie C , Zhang K , Zhu X , Chen J , Huang H
Ref : Cell Death Dis , 12 :992 , 2021
Abstract : Vascular calcification is common in chronic kidney disease (CKD) and contributes to cardiovascular disease (CVD) without any effective therapies available up to date. The expression of soluble epoxide hydrolase (sEH) is different in patients with and without vascular calcification. The present study investigates the role of sEH as a potential mediator of vascular calcification in CKD. Both Ephx2(-)(/-) and wild-type (WT) mice fed with high adenine and phosphate (AP) diet were used to explore the vascular calcification in CKD. Compared with WT, deletion of sEH inhibited vascular calcification induced by AP. sEH deletion also abolished high phosphorus (Pi)-induced phenotypic transition of vascular smooth muscle cells (VSMCs) independent of its epoxyeicosatrienoic acids (EETs) hydrolysis. Further gene expression analysis identified the potential role of Sirtuin 3 (Sirt3) in the sEH-regulated VSMC calcification. Under high Pi treatment, sEH interacted with Sirt3, which might destabilize Sirt3 and accelerate the degradation of Sirt3. Deletion of sEH may preserve the expression of Sirt3, and thus maintain the mitochondrial adenosine triphosphate (ATP) synthesis and morphology, significantly suppressing VSMC calcification. Our data supported that sEH deletion inhibited vascular calcification and indicated a promising target of sEH inhibition in vascular calcification prevention.
ESTHER : He_2021_Cell.Death.Dis_12_992
PubMedSearch : He_2021_Cell.Death.Dis_12_992
PubMedID: 34689162

Title : In Vitro and In Vivo Anti-AChE and Antioxidative Effects of Schisandra chinensis Extract: A Potential Candidate for Alzheimer's Disease - Song_2020_Evid.Based.Complement.Alternat.Med_2020_2804849
Author(s) : Song X , Wang T , Guo L , Jin Y , Wang J , Yin G , Jiang K , Wang L , Huang H , Zeng L
Ref : Evid Based Complement Alternat Med , 2020 :2804849 , 2020
Abstract : Acetylcholinesterase (AChE) inhibition and antioxidants are two common strategies for the treatment in the early stage of Alzheimer's Disease (AD). In this study, extracts from nine traditional Chinese medical (TCM) herbs were tested for anti-AChE activity by Ellman's microplate assay and cytotoxicity by CCK-8. Based on its excellent AChE inhibition effect and its lowest cytotoxicity, Schisandra chinensis (SC) extract was selected to do the mechanism research. SC extract protected pheochromocytoma (PC12) cells against H2O2-induced toxicity by improving the cell survival rate in a dose-dependent manner. And it also showed significant free radical (DPPH) scavenging activities, ferric reducing antioxidant power (FRAP), and 2,2'-Azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging. To confirm these results, the scopolamine-induced mice models were utilized in this study. Compared with the positive drug (piracetam), SC could also exhibit similar effects to alleviate the mice's cognitive deficits. Moreover, in the mice brain samples, the AChE activity and malondialdehyde (MDA) levels of SC-treatment group both showed a reverse as compared to model group. Taken together, these results all suggested that SC extract may be a potential therapeutic candidate for AD.
ESTHER : Song_2020_Evid.Based.Complement.Alternat.Med_2020_2804849
PubMedSearch : Song_2020_Evid.Based.Complement.Alternat.Med_2020_2804849
PubMedID: 32148536

Title : Anti-tubercular derivatives of rhein require activation by the monoglyceride lipase Rv0183 - Abrahams_2020_Cell.Surf_6_100040
Author(s) : Abrahams KA , Hu W , Li G , Lu Y , Richardson EJ , Loman NJ , Huang H , Besra GS
Ref : Cell Surf , 6 :100040 , 2020
Abstract : The emergence and perseverance of drug resistant strains of Mycobacterium tuberculosis (Mtb) ensures that drug discovery efforts remain at the forefront of tuberculosis research. There are numerous different approaches that can be employed to lead to the discovery of anti-tubercular agents. In this work, we endeavored to optimize the anthraquinone chemical scaffold of a known drug, rhein, converting it from a compound with negligible activity against Mtb, to a series of compounds with potent activity. Two compounds exhibited low toxicity and good liver microsome stability and were further progressed in attempts to identify the biological target. Whole genome sequencing of resistant isolates revealed inactivating mutations in a monoglyceride lipase. Over-expression trials and an enzyme assay confirmed that the designed compounds are prodrugs, activated by the monoglyceride lipase. We propose that rhein is the active moiety of the novel compounds, which requires chemical modifications to enable access to the cell through the extensive cell wall structure. This work demonstrates that re-engineering of existing antimicrobial agents is a valid method in the development of new anti-tubercular compounds.
ESTHER : Abrahams_2020_Cell.Surf_6_100040
PubMedSearch : Abrahams_2020_Cell.Surf_6_100040
PubMedID: 32743152
Gene_locus related to this paper: myctu-rv0183

Title : Lysosome targeting metal-organic framework probe LysFP@ZIF-8 for highly sensitive quantification of carboxylesterase 1 and organophosphates in living cells - Shen_2020_J.Hazard.Mater__124342
Author(s) : Shen B , Zhang X , Dai J , Ji Y , Huang H
Ref : J Hazard Mater , :124342 , 2020
Abstract : Herein, a lysosomal targeting LysFP@ZIF-8 metal-organic framework (MOF) was fabricated using fluorescent protein chromophore-based probe (LysFP) for selectively detection of carboxylesterase 1 (CES1) in living cells. Unlike the regular small molecule fluorescent probes, LysFP@ZIF-8 showed wide range pH tolerabiligy, high selectivity and sensitivity to CES1 in bio-samples, and was successfully applied to achieve the visual monitoring of CES1 activity in living cells. Low detection limit and high fluorescence quantum yield was calculated as 79 ng/mL and 0.76 for LysFP@ZIF-8, respectively. Furthermore, LysFP@ZIF-8 can also serve as a fluorescence indicator of organophosphates pesticide exposure in the way of hydrolyzing the carboxylic acid ester group in LysFP. This type of probe can inspire the development of fluorescent tools for further explore many pathological processes.
ESTHER : Shen_2020_J.Hazard.Mater__124342
PubMedSearch : Shen_2020_J.Hazard.Mater__124342
PubMedID: 33257119

Title : Biochemical Characterization and Mutational Analysis of a Lactone Hydrolase from Phialophora americana - Yu_2020_J.Agric.Food.Chem_68_2570
Author(s) : Yu X , Tu T , Luo H , Huang H , Su X , Wang Y , Zhang J , Bai Y , Yao B
Ref : Journal of Agricultural and Food Chemistry , 68 :2570 , 2020
Abstract : The mycotoxin zearalenone (ZEN) is a secondary metabolite produced mainly by Fusarium species. ZEN poses health hazards both for humans and animals, as a major contaminant in the food and feed industries. Currently, there is no effective technique for degrading ZEN during industrial processes. In this study, we isolated and biochemically characterized a novel lactone hydrolase, ZHD607, isolated from Phialophora americana, cloned, and exogenously expressed in Pichia pastoris. ZHD607 was characterized as a mesophilic lactone hydrolase having a neutral pH and showing optimal activity at 35 degreesC and pH 8.0. Two mutants, ZHDM1 and I160Y, generated from ZHD607 based on structure and sequence alignment analyses, exhibited 2.9- and 3.4-fold higher activity towards ZEN than did ZHD607. Molecular dynamics simulation revealed diverse mechanisms driving this improved catalytic activity. These findings enrich our knowledge about ZHD enzyme family and represent an important step toward industrialization of ZEN-detoxifying lactone hydrolases.
ESTHER : Yu_2020_J.Agric.Food.Chem_68_2570
PubMedSearch : Yu_2020_J.Agric.Food.Chem_68_2570
PubMedID: 31760747
Gene_locus related to this paper: 9euro-a0a0d2e8j6

Title : Integration of lipidomic and transcriptomic profiles reveals novel genes and regulatory mechanisms of Schizochytrium sp. in response to salt stress - Jiang_2019_Bioresour.Technol_294_122231
Author(s) : Jiang JY , Zhu S , Zhang Y , Sun X , Hu X , Huang H , Ren LJ
Ref : Bioresour Technol , 294 :122231 , 2019
Abstract : In this study, the effects of salt stress on the physiological, lipidomic and transcriptomic profiles of halophilic microalga Schizochytrium sp. were investigated. In general, Schizochytrium sp. could survive under high osmotic fermentation medium containing 30g/L NaCl, and showed a significant increase in C14:0 percentage in total fatty acids. In lipidomic analysis, C14:0 was specifically enriched in phosphatidylcholine (PC), and membrane phospholipids participated in the salt stress response mostly. Specially, one novel signal lipid N-acylphosphatidylethanolamine (NAPE) (18:0/20:3/14:0) was upregulated significantly. Transcriptomic analysis revealed glycerol-3-phosphate acyltransferase (GPAT) and phospholipase ABHD3 (PLABDH3) were involved in C14:0 metabolism and NAPE biosynthesis. Signalling pathways they mediated were activated as evident by high expression level of Myristoyl-CoA: protein N-myristoyltransferase (NMT) and NAPE-hydrolyzing PLD (NAPE-PLD). This study gives us an insight in specific responses to salt stress in Schizochytrium sp. and provides a considerable proportion of novel genes that could commendably be used for engineering modification.
ESTHER : Jiang_2019_Bioresour.Technol_294_122231
PubMedSearch : Jiang_2019_Bioresour.Technol_294_122231
PubMedID: 31606596

Title : Structural Basis of Fullerene Derivatives as Novel Potent Inhibitors of Protein Acetylcholinesterase without Catalytic Active Site Interaction: Insight into the Inhibitory Mechanism through Molecular Modeling Studies - Wan_2019_J.Biomol.Struct.Dyn__1
Author(s) : Wan Y , Guan S , Qian M , Huang H , Han F , Wang S , Zhang H
Ref : J Biomol Struct Dyn , :1 , 2019
Abstract : Acetylcholinesterase (AChE) is an important kind of esterase that plays a key biological role in the central and peripheral nervous system. Recent research has demonstrated that some fullerene derivatives serve as a new nanoscale-class of potent inhibitors of AChE, but the specific inhibition mechanism remains unclear. In the present article, several molecular modeling methods, such as molecular docking, molecular dynamics simulations, and molecular mechanics/generalized Born surface area calculations, were used for the investigation of the binding mode and inhibition mechanism of fullerene inhibitions for AChE. Results revealed that fullerene inhibitors block the entrance of substrates by binding with the peripheral anionic site (PAS) region. Thus, fullerene derivatives might mainly serve as competitive inhibitors. The - interactions of a fullerene backbone with AChE are at the same level in different single side chain systems and seem to be related to the length or aromaticity of the side chain. The inhibitor with multi hydroxyl side chains shows an obviously large electrostatic interaction as it forms additional hydrogen bonds with AChE. Moreover, fullerene derivatives might exhibit noncompetitive inhibition partly by affecting some secondary structures around them. Thus, the destructions of these secondary structures can lead to conformational changes in some important regions, such as the catalytic triad and acyl pocket. The investigation is of great importance to the discovery of good fullerene inhibitors.
ESTHER : Wan_2019_J.Biomol.Struct.Dyn__1
PubMedSearch : Wan_2019_J.Biomol.Struct.Dyn__1
PubMedID: 30706763

Title : Synthesis of functional ionic liquid modified magnetic chitosan nanoparticles for porcine pancreatic lipase immobilization - Suo_2019_Mater.Sci.Eng.C.Mater.Biol.Appl_96_356
Author(s) : Suo H , Gao Z , Xu L , Xu C , Yu D , Xiang X , Huang H , Hu Y
Ref : Mater Sci Eng C Mater Biol Appl , 96 :356 , 2019
Abstract : We developed magnetic chitosan nanoparticles (CSFe3O4) with mean diameter of 15-20nm. Subsequently, these inorganic-organic composite nanoparticles were modified using an imidazole-based functional ionic liquid (IL). The prepared support (ILCSFe3O4), which was used to immobilize porcine pancreatic lipase (PPL), was characterized using Fourier transform infrared (FTIR) spectroscopy, vibrating sample magnetometry (VSM), thermogravimetry (TG), transmission electron microscopy (TEM) and X-ray diffraction (XRD). Circular dichroism (CD) was used to analyze the secondary structure of immobilized PPL. The immobilized PPL (PPLILCSFe3O4) exhibited 1.93-fold higher specific activity than PPLCS-Fe3O4 when triacetin was used as the substrate, and showed 95mg/g of lipase immobilization capacity and 382% of activity recovery. The residual activity of PPLILCSFe3O4 was above 60% of the initial activity after incubation at 50 degrees C for 6h, as was higher than that of PPLCSFe3O4 which showed 40% of the initial activity. In addition, PPLILCSFe3O4 retained 84.6% of the initial activity after 10cycles, whereas PPLCSFe3O4 retained only 75.5% activity. Furthermore, the kinetic parameters, apparent Km and Vmax of PPLILCSFe3O4 were 2.51mg/mL and 1.395U/mg respectively, these results indicated that the immobilized PPL had better affinity towards the substrate, especially when the nanoparticles were modified by functional IL. Besides, the magnetic chitosan nanoparticles loaded with PPL were easily recovered. A novel, efficient, and practical method for enzyme immobilization was developed.
ESTHER : Suo_2019_Mater.Sci.Eng.C.Mater.Biol.Appl_96_356
PubMedSearch : Suo_2019_Mater.Sci.Eng.C.Mater.Biol.Appl_96_356
PubMedID: 30606543

Title : Interesterification of rice bran wax and palm olein catalyzed by lipase: Crystallization behaviours and characterization - Zhang_2019_Food.Chem_286_29
Author(s) : Zhang Z , Ye J , Fei T , Ma X , Xie X , Huang H , Wang Y
Ref : Food Chem , 286 :29 , 2019
Abstract : Rice bran wax (RBW) is a traditional plant based natural wax and an increasingly popular component in textiles, fruit coatings and cosmetics. Properties of RBW can be modified by acyglycerols, and the resulting products can possess features with great potential in different applications. In this study, RBW was interesterified with palm olein (POL) catalyzed by Lipozyme TL IM, and the effects of RBW on the crystallization rate, solid fat content (SFC) and thermodynamic properties were investigated. The crystallization rates of RBW-based enzymatically interesterified (EIE) products were significantly higher than both the starting mixture and fully hydrogenated rapeseed oil (FHRSO). The EIE RBW-based samples were predominantly crystallized in beta' form, and presented a much smoother SFC profile as compared to physically blended raw materials. The SFC values were significantly decreased, conversely increased, and remained constant, and at 10 degreeC, 20-30 degreeC, and 35-40 degreeC as the wax ester and acylglycerols compositions changes. Overall, RBW-based samples after EIE showed an increased hardness and good surface properties, which make it a potential plastic fats substitute.
ESTHER : Zhang_2019_Food.Chem_286_29
PubMedSearch : Zhang_2019_Food.Chem_286_29
PubMedID: 30827609

Title : Biodegradation of Structurally Diverse Phthalate Esters by a Newly Identified Esterase with Catalytic Activity toward Di(2-ethylhexyl) Phthalate - Huang_2019_J.Agric.Food.Chem_67_8548
Author(s) : Huang H , Zhang XY , Chen TL , Zhao YL , Xu DS , Bai YP
Ref : Journal of Agricultural and Food Chemistry , 67 :8548 , 2019
Abstract : Herein, we report a double enzyme system to degrade 12 phthalate esters (PAEs), particularly bulky PAEs, such as the widely used bis(2-ethylhexyl) phthalate (DEHP), in a one-pot cascade process. A PAE-degrading bacterium, Gordonia sp. strain 5F, was isolated from soil polluted with plastic waste. From this strain, a novel esterase (GoEst15) and a mono(2-ethylhexyl) phthalate hydrolase (GoEstM1) were identified by homology-based cloning. GoEst15 showed broad substrate specificity, hydrolyzing DEHP and 10 other PAEs to monoalkyl phthalates, which were further degraded by GoEstM1 to phthalic acid. GoEst15 and GoEstM1 were heterologously coexpressed in Escherichia coli BL21 (DE3), which could then completely degrade 12 PAEs (5 mM), within 1 and 24 h for small and bulky substrates, respectively. To our knowledge, GoEst15 is the first DEHP hydrolase with a known protein sequence, which will enable protein engineering to enhance its catalytic performance in the future.
ESTHER : Huang_2019_J.Agric.Food.Chem_67_8548
PubMedSearch : Huang_2019_J.Agric.Food.Chem_67_8548
PubMedID: 31266305
Gene_locus related to this paper: gorpv-h6n0g6

Title : Enhanced catalytic performance of lipase covalently bonded on ionic liquids modified magnetic alginate composites - Suo_2019_J.Colloid.Interface.Sci_553_494
Author(s) : Suo H , Xu L , Xu C , Qiu X , Huang H , Hu Y
Ref : J Colloid Interface Sci , 553 :494 , 2019
Abstract : We prepared ionic liquids (ILs) modified magnetic alginate nanoparticles and used these as supports for lipase immobilization. The novel supports were characterized using Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance ((1)HNMR), vibrating sample magnetometry (VSM), thermogravimetry (TG), transmission electron microscopy (TEM) and water contact angle (WCA) measurements. The immobilized lipase (PPL-IL-MSA) exhibited high activity, 2.1-fold higher than that compared to free lipase and 1.59-fold higher compared to immobilized lipase without IL (PPL-MSA). In addition, the pH and temperature application range of PPL-IL-MSA were both found to be broader than that of free lipase and PPL-MSA. The thermal stability, denaturation stability, and reusing stability of PPL-IL-MSA were also higher than those of other samples. After 10 times of reuse, the residual activity of PPL-IL-MSA was 89.7% higher than that of PPL-MSA (84.4%). Furthermore, the kinetic constant Km of PPL-IL-MSA was 13.7mg/mL lower than that of free lipase (21.2mg/mL) and PPL-MSA (18.4mg/mL). Circular dichroism (CD) was used to study the secondary structure of enzymes in order to explain the mechanism of the performance improvement of PPL-IL-MSA. This work involving the development of a new supports for enzyme immobilization may serve as a reference for further studies in this field.
ESTHER : Suo_2019_J.Colloid.Interface.Sci_553_494
PubMedSearch : Suo_2019_J.Colloid.Interface.Sci_553_494
PubMedID: 31229868

Title : Effects of fasting on the activities and mRNA expression levels of lipoprotein lipase (LPL), hormone-sensitive lipase (HSL) and fatty acid synthetase (FAS) in spotted seabass Lateolabrax maculatus - Huang_2018_Fish.Physiol.Biochem_44_387
Author(s) : Huang H , Zhang Y , Cao M , Xue L , Shen W
Ref : Fish Physiol Biochem , 44 :387 , 2018
Abstract : To investigate the effects of fasting on lipid metabolism in spotted seabass muscle and liver tissues, we analyzed mRNA levels and enzyme activities of lipoprotein lipase (LPL), hormone-sensitive lipase (HSL) and fatty acid synthetase (FAS), and the relationship among fat content, mRNA level, and enzyme activity during fasting of 35 days. The results showed that expressions of all the three genes were ubiquitous. During the fasting experiment, the hepatosomatic index (HSI) and fat content of muscle and liver tissues significantly decreased before 5 days of fasting (P < 0.05). mRNA levels of LPL increased significantly after 5 days of fasting in liver and 7 days in muscle. Abundance of HSL transcripts increased significantly after 14 days of fasting in both muscle and liver. The activities of LPL and HSL presented a trend that increased firstly, decreased subsequently, and then raised again with the prolonged fasting experiment (P < 0.05). However, activities and mRNA levels of FAS decreased significantly after 1 day of fasting in both muscle and liver. Moreover, activities and mRNA levels of FAS showed a moderate correlation in muscle. These results suggested that FAS had a sooner response to fasting than LPL and HSL in both muscle and liver tissues. LPL and HSL played important roles in lipolysis mainly by increasing enzyme activities in the early stage of fasting and mRNA levels in the later stage of fasting in both muscle and liver. Our results also provided useful information on regulating muscle fat content by fasting.
ESTHER : Huang_2018_Fish.Physiol.Biochem_44_387
PubMedSearch : Huang_2018_Fish.Physiol.Biochem_44_387
PubMedID: 29147968

Title : Effects of Distal Mutations on the Structure, Dynamics and Catalysis of Human Monoacylglycerol Lipase - Tyukhtenko_2018_Sci.Rep_8_1719
Author(s) : Tyukhtenko S , Rajarshi G , Karageorgos I , Zvonok N , Gallagher ES , Huang H , Vemuri K , Hudgens JW , Ma X , Nasr ML , Pavlopoulos S , Makriyannis A
Ref : Sci Rep , 8 :1719 , 2018
Abstract : An understanding of how conformational dynamics modulates function and catalysis of human monoacylglycerol lipase (hMGL), an important pharmaceutical target, can facilitate the development of novel ligands with potential therapeutic value. Here, we report the discovery and characterization of an allosteric, regulatory hMGL site comprised of residues Trp-289 and Leu-232 that reside over 18 A away from the catalytic triad. These residues were identified as critical mediators of long-range communication and as important contributors to the integrity of the hMGL structure. Nonconservative replacements of Trp-289 or Leu-232 triggered concerted motions of structurally distinct regions with a significant conformational shift toward inactive states and dramatic loss in catalytic efficiency of the enzyme. Using a multimethod approach, we show that the dynamically relevant Trp-289 and Leu-232 residues serve as communication hubs within an allosteric protein network that controls signal propagation to the active site, and thus, regulates active-inactive interconversion of hMGL. Our findings provide new insights into the mechanism of allosteric regulation of lipase activity, in general, and may provide alternative drug design possibilities.
ESTHER : Tyukhtenko_2018_Sci.Rep_8_1719
PubMedSearch : Tyukhtenko_2018_Sci.Rep_8_1719
PubMedID: 29379013
Gene_locus related to this paper: human-MGLL

Title : Impact of Fabp1 Gene Ablation on Uptake and Degradation of Endocannabinoids in Mouse Hepatocytes - McIntosh_2018_Lipids_53_561
Author(s) : McIntosh AL , Huang H , Landrock D , Martin GG , Li S , Kier AB , Schroeder F
Ref : Lipids , 53 :561 , 2018
Abstract : Liver fatty-acid-binding protein (FABP1, L-FABP) is the major cytosolic binding/chaperone protein for both precursor arachidonic acid (ARA) and the endocannabinoid (EC) products N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG). Although FABP1 regulates hepatic uptake and metabolism of ARA, almost nothing is known regarding FABP1's impact on AEA and 2-AG uptake, intracellular distribution, and targeting of AEA and 2-AG to degradative hepatic enzymes. In vitro assays revealed that FABP1 considerably enhanced monoacylglycerol lipase hydrolysis of 2-AG but only modestly enhanced AEA hydrolysis by fatty-acid amide hydrolase. Conversely, liquid chromatography-mass spectrometry of lipids from Fabp1 gene-ablated (LKO) hepatocytes confirmed that loss of FABP1 markedly diminished hydrolysis of 2-AG. Furthermore, the real-time imaging of novel fluorescent NBD-labeled probes (NBD-AEA, NBD-2-AG, and NBD-ARA) resolved FABP1's impact on uptake vs intracellular targeting/hydrolysis. FABP1 bound NBD-ARA with 2:1 stoichiometry analogous to ARA, but bound NBD-2-AG and NBD-AEA with 1:1 stoichiometry-apparently at different sites in FABP1's binding cavity. All three probes were taken up, but NBD-2-AG and NBD-AEA were targeted to lipid droplets. LKO reduced the uptake of NBD-ARA as expected, significantly enhanced that of NBD-AEA, but had little effect on NBD-2-AG. These data indicated that FABP1 impacts hepatocyte EC levels by binding EC and differentially impacts their intracellular hydrolysis (2-AG) and uptake (AEA).
ESTHER : McIntosh_2018_Lipids_53_561
PubMedSearch : McIntosh_2018_Lipids_53_561
PubMedID: 30203570

Title : A manually annotated Actinidia chinensis var. chinensis (kiwifruit) genome highlights the challenges associated with draft genomes and gene prediction in plants - Pilkington_2018_BMC.Genomics_19_257
Author(s) : Pilkington SM , Crowhurst R , Hilario E , Nardozza S , Fraser L , Peng Y , Gunaseelan K , Simpson R , Tahir J , Deroles SC , Templeton K , Luo Z , Davy M , Cheng C , McNeilage M , Scaglione D , Liu Y , Zhang Q , Datson P , De Silva N , Gardiner SE , Bassett H , Chagne D , McCallum J , Dzierzon H , Deng C , Wang YY , Barron L , Manako K , Bowen J , Foster TM , Erridge ZA , Tiffin H , Waite CN , Davies KM , Grierson EP , Laing WA , Kirk R , Chen X , Wood M , Montefiori M , Brummell DA , Schwinn KE , Catanach A , Fullerton C , Li D , Meiyalaghan S , Nieuwenhuizen N , Read N , Prakash R , Hunter D , Zhang H , McKenzie M , Knabel M , Harris A , Allan AC , Gleave A , Chen A , Janssen BJ , Plunkett B , Ampomah-Dwamena C , Voogd C , Leif D , Lafferty D , Souleyre EJF , Varkonyi-Gasic E , Gambi F , Hanley J , Yao JL , Cheung J , David KM , Warren B , Marsh K , Snowden KC , Lin-Wang K , Brian L , Martinez-Sanchez M , Wang M , Ileperuma N , Macnee N , Campin R , McAtee P , Drummond RSM , Espley RV , Ireland HS , Wu R , Atkinson RG , Karunairetnam S , Bulley S , Chunkath S , Hanley Z , Storey R , Thrimawithana AH , Thomson S , David C , Testolin R , Huang H , Hellens RP , Schaffer RJ
Ref : BMC Genomics , 19 :257 , 2018
Abstract : BACKGROUND: Most published genome sequences are drafts, and most are dominated by computational gene prediction. Draft genomes typically incorporate considerable sequence data that are not assigned to chromosomes, and predicted genes without quality confidence measures. The current Actinidia chinensis (kiwifruit) 'Hongyang' draft genome has 164 Mb of sequences unassigned to pseudo-chromosomes, and omissions have been identified in the gene models. RESULTS: A second genome of an A. chinensis (genotype Red5) was fully sequenced. This new sequence resulted in a 554.0 Mb assembly with all but 6 Mb assigned to pseudo-chromosomes. Pseudo-chromosomal comparisons showed a considerable number of translocation events have occurred following a whole genome duplication (WGD) event some consistent with centromeric Robertsonian-like translocations. RNA sequencing data from 12 tissues and ab initio analysis informed a genome-wide manual annotation, using the WebApollo tool. In total, 33,044 gene loci represented by 33,123 isoforms were identified, named and tagged for quality of evidential support. Of these 3114 (9.4%) were identical to a protein within 'Hongyang' The Kiwifruit Information Resource (KIR v2). Some proportion of the differences will be varietal polymorphisms. However, as most computationally predicted Red5 models required manual re-annotation this proportion is expected to be small. The quality of the new gene models was tested by fully sequencing 550 cloned 'Hort16A' cDNAs and comparing with the predicted protein models for Red5 and both the original 'Hongyang' assembly and the revised annotation from KIR v2. Only 48.9% and 63.5% of the cDNAs had a match with 90% identity or better to the original and revised 'Hongyang' annotation, respectively, compared with 90.9% to the Red5 models. CONCLUSIONS: Our study highlights the need to take a cautious approach to draft genomes and computationally predicted genes. Our use of the manual annotation tool WebApollo facilitated manual checking and correction of gene models enabling improvement of computational prediction. This utility was especially relevant for certain types of gene families such as the EXPANSIN like genes. Finally, this high quality gene set will supply the kiwifruit and general plant community with a new tool for genomics and other comparative analysis.
ESTHER : Pilkington_2018_BMC.Genomics_19_257
PubMedSearch : Pilkington_2018_BMC.Genomics_19_257
PubMedID: 29661190
Gene_locus related to this paper: actde-CXE3 , actde-CXE5 , actch-a0a2r6p9v4 , actch-a0a2r6phk8 , actch-a0a2r6pty2 , actch-q0zpu6 , actcc-a0a2r6q553 , actcc-a0a2r6quq2 , actcc-a0a2r6q2m9 , actcc-a0a2r6q2n7 , actcc-a0a2r6ru97 , actcc-a0a2r6r3e8 , actcc-a0a2r6qy24 , actcc-a0a2r6pzy5 , actcc-a0a2r6p5n3 , actcc-a0a2r6qdp0 , actcc-a0a2r6qgs9

Title : Hydrogen peroxide redistributes the localization of protein phosphatase methylesterase 1 - Tang_2018_Life.Sci_213_166
Author(s) : Tang S , Lu C , Mo L , Wang X , Liang Z , Qin F , Liu Y , Huang H , Huang Y , Cai H , Xiao D , Guo S , Ouyang Y , Sun B , Li X
Ref : Life Sciences , 213 :166 , 2018
Abstract : AIMS: Protein phosphatase methylesterase-1 (PME-1) is a serine hydrolase that catalyzes protein phosphatase 2A (PP2A) demethylation and negatively regulates its activity. PME-1 is compartmentalized within cells to precisely control the demethylation of PP2A. This study investigated the localization of PME-1 in human fibroblast cells (HDF) under oxidative stress. MAIN METHODS: Alkaline demethylation and peptide competition assays were applied to detect the methylation sensitivity of anti-PP2Ac. The localization of PME-1, leucine carboxyl methyltransferase 1 (LCMT1), demethylated-phosphorylated-PP2Ac (dem-p-PP2Ac) and total PP2Ac was determined by immunofluorescence analysis, and protein expression was measured by Western blot. A HEK293 cell line stably expressing constructed PME-1-EGFP was used to dynamically monitor the nuclear export of PME-1 under oxidative stress. KEY RESULTS: After hydrogen peroxide (H(2)O(2)) treatment, the protein expression of PME-1 remained unchanged, while PME-1 facilitated redistribution from the nucleus to the cytoplasm in HDF according to immunofluorescence analysis. In constructed HEK293 cells, the EGFP-tagged PME-1 was exported from the nucleus to the cytoplasm after H(2)O(2) treatment, and nuclear export was eliminated after leptomycin B additions. Our observation of dem-p-PP2Ac species relocation from the nucleus to the cytoplasm under oxidative stress is consistent with the redistribution patterns of PME-1. Antioxidant N-acetyl cysteine can reverse the nuclear to cytoplasmic ratio of PME-1 proteins and dem-p-PP2Ac after H(2)O(2) exposure. SIGNIFICANCE: We found that PME-1 is exported from the nucleus to the cytoplasm upon H(2)O(2) treatment and redistributes dem-p-PP2Ac in subcellular compartments. These findings offer new insight into the regulation of PME-1 localization and PP2A demethylation under oxidative stress.
ESTHER : Tang_2018_Life.Sci_213_166
PubMedSearch : Tang_2018_Life.Sci_213_166
PubMedID: 30340029
Gene_locus related to this paper: human-PPME1

Title : Protein Bioinformatics Databases and Resources - Chen_2017_Methods.Mol.Biol_1558_3
Author(s) : Chen C , Huang H , Wu CH
Ref : Methods Mol Biol , 1558 :3 , 2017
Abstract : Many publicly available data repositories and resources have been developed to support protein-related information management, data-driven hypothesis generation, and biological knowledge discovery. To help researchers quickly find the appropriate protein-related informatics resources, we present a comprehensive review (with categorization and description) of major protein bioinformatics databases in this chapter. We also discuss the challenges and opportunities for developing next-generation protein bioinformatics databases and resources to support data integration and data analytics in the Big Data era.
ESTHER : Chen_2017_Methods.Mol.Biol_1558_3
PubMedSearch : Chen_2017_Methods.Mol.Biol_1558_3
PubMedID: 28150231

Title : The dual DPP4 inhibitor and GPR119 agonist HBK001 regulates glycemic control and beta cell function ex and in vivo - Huan_2017_Sci.Rep_7_4351
Author(s) : Huan Y , Jiang Q , Li G , Bai G , Zhou T , Liu S , Li C , Liu Q , Sun S , Yang M , Guo N , Wang X , Wang S , Liu Y , Wang G , Huang H , Shen Z
Ref : Sci Rep , 7 :4351 , 2017
Abstract : Glucagon like peptide-1 (GLP-1) plays a vital role in glucose homeostasis and sustaining beta-cell function. Currently there are two major methods to enhance endogenous GLP-1 activity; inhibiting dipeptidyl peptidase-4 (DPP4) or activating G protein-coupled receptor 119 (GPR119). Here we describe and validate a novel dual-target compound, HBK001, which can both inhibit DPP4 and activate GPR119 ex and in vivo. We show that HBK001 can promote glucose-stimulated insulin secretion in mouse and human primary islets. A single administration of HBK001 in ICR mice can increase plasma incretins levels much more efficiently than linagliptin, a classic DPP4 inhibitor. Long-term treatment of HBK001 in KKAy mice can ameliorate hyperglycemia as well as improve glucose tolerance, while linagliptin fails to achieve such glucose-lowing effects despite inhibiting 95% of serum DPP4 activity. Moreover, HBK001 can increase first-phase insulin secretion in KKAy mice, suggesting a direct effect on islet beta-cells via GPR119 activation. Furthermore, HBK001 can improve islet morphology, increase beta-cell proliferation and up-regulate genes involved in improved beta-cell function. Thus, we have identified, designed and synthesized a novel dual-target compound, HBK001, which represents a promising therapeutic candidate for type 2 diabetes, especially for patients who are insensitive to current DPP4 inhibitors.
ESTHER : Huan_2017_Sci.Rep_7_4351
PubMedSearch : Huan_2017_Sci.Rep_7_4351
PubMedID: 28659588

Title : Growth of Thalamocortical Fibers to the Somatosensory Cortex in the Human Fetal Brain - Krsnik_2017_Front.Neurosci_11_233
Author(s) : Krsnik Z , Majic V , Vasung L , Huang H , Kostovic I
Ref : Front Neurosci , 11 :233 , 2017
Abstract : Thalamocortical (TH-C) fiber growth begins during the embryonic period and is completed by the third trimester of gestation in humans. Here we determined the timing and trajectories of somatosensory TH-C fibers in the developing human brain. We analyzed the periods of TH-C fiber outgrowth, path-finding, "waiting" in the subplate (SP), target selection, and ingrowth in the cortical plate (CP) using histological sections from post-mortem fetal brain [from 7 to 34 postconceptional weeks (PCW)] that were processed with acetylcholinesterase (AChE) histochemistry and immunohistochemical methods. Images were compared with post mortem diffusion tensor imaging (DTI)-based fiber tractography (code No NO1-HD-4-3368). The results showed TH-C axon outgrowth occurs as early as 7.5 PCW in the ventrolateral part of the thalamic anlage. Between 8 and 9.5 PCW, TH-C axons form massive bundles that traverse the diencephalic-telencephalic boundary. From 9.5 to 11 PCW, thalamocortical axons pass the periventricular area at the pallial-subpallial boundary and enter intermediate zone in radiating fashion. Between 12 and 14 PCW, the TH-C axons, aligned along the fibers from the basal forebrain, continue to grow for a short distance within the deep intermediate zone and enter the deep CP, parallel with SP expansion. Between 14 and 18 PCW, the TH-C interdigitate with callosal fibers, running shortly in the sagittal stratum and spreading through the deep SP ("waiting" phase). From 19 to 22 PCW, TH-C axons accumulate in the superficial SP below the somatosensory cortical area; this occurs 2 weeks earlier than in the frontal and occipital cortices. Between 23 and 24 PCW, AChE-reactive TH-C axons penetrate the CP concomitantly with its initial lamination. Between 25 and 34 PCW, AChE reactivity of the CP exhibits an uneven pattern suggestive of vertical banding, showing a basic 6-layer pattern. In conclusion, human thalamocortical axons show prolonged growth (4 months), and somatosensory fibers precede the ingrowth of fibers destined for frontal and occipital areas. The major features of growing TH-C somatosensory fiber trajectories are fan-like radiation, short runs in the sagittal strata, and interdigitation with the callosal system. These results support our hypothesis that TH-C axons are early factors in SP and CP morphogenesis and synaptogenesis and may regulate cortical somatosensory system maturation.
ESTHER : Krsnik_2017_Front.Neurosci_11_233
PubMedSearch : Krsnik_2017_Front.Neurosci_11_233
PubMedID: 28496398

Title : The Dendrobium catenatum Lindl. genome sequence provides insights into polysaccharide synthase, floral development and adaptive evolution - Zhang_2016_Sci.Rep_6_19029
Author(s) : Zhang GQ , Xu Q , Bian C , Tsai WC , Yeh CM , Liu KW , Yoshida K , Zhang LS , Chang SB , Chen F , Shi Y , Su YY , Zhang YQ , Chen LJ , Yin Y , Lin M , Huang H , Deng H , Wang ZW , Zhu SL , Zhao X , Deng C , Niu SC , Huang J , Wang M , Liu GH , Yang HJ , Xiao XJ , Hsiao YY , Wu WL , Chen YY , Mitsuda N , Ohme-Takagi M , Luo YB , Van de Peer Y , Liu ZJ
Ref : Sci Rep , 6 :19029 , 2016
Abstract : Orchids make up about 10% of all seed plant species, have great economical value, and are of specific scientific interest because of their renowned flowers and ecological adaptations. Here, we report the first draft genome sequence of a lithophytic orchid, Dendrobium catenatum. We predict 28,910 protein-coding genes, and find evidence of a whole genome duplication shared with Phalaenopsis. We observed the expansion of many resistance-related genes, suggesting a powerful immune system responsible for adaptation to a wide range of ecological niches. We also discovered extensive duplication of genes involved in glucomannan synthase activities, likely related to the synthesis of medicinal polysaccharides. Expansion of MADS-box gene clades ANR1, StMADS11, and MIKC(*), involved in the regulation of development and growth, suggests that these expansions are associated with the astonishing diversity of plant architecture in the genus Dendrobium. On the contrary, members of the type I MADS box gene family are missing, which might explain the loss of the endospermous seed. The findings reported here will be important for future studies into polysaccharide synthesis, adaptations to diverse environments and flower architecture of Orchidaceae.
ESTHER : Zhang_2016_Sci.Rep_6_19029
PubMedSearch : Zhang_2016_Sci.Rep_6_19029
PubMedID: 26754549
Gene_locus related to this paper: 9aspa-a0a2i0w093 , 9aspa-a0a2i0vyy1 , 9aspa-a0a2i0x5j6 , 9aspa-a0a2i0win6 , 9aspa-a0a2i0vg82

Title : Screening of soluble epoxide hydrolase inhibitory ingredients from traditional Chinese medicines for anti-inflammatory use - Liu_2016_J.Ethnopharmacol_194_475
Author(s) : Liu JY , Morisseau C , Huang H , Hammock BD
Ref : J Ethnopharmacol , 194 :475 , 2016
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Inhibition of soluble epoxide hydrolase (sEH) has been extensively reported to be anti-inflammatory in multiple animal models. Some anti-inflammatory traditional Chinese medicines (TCMs) and a few natural compounds were also found to be inhibitory to sEH in vitro. AIM OF THE STUDY: To determine whether the active intergradient (AI) against sEH of anti-inflammatory TCMs in vitro is anti-inflammatory in vivo and the sEH inhibitory action of the AI contributes to its anti-inflammatory effect in vivo. MATERIALS AND
METHODS: In vitro inhibition assay of the sEH was conducted for the methanol and ethanol extracts of 27 anti-inflammatory TCMs. Two potent extracts were subject to further separation guided by bioassay to afford promising AI against sEH in vitro [Fr.5 of the crude ethanol extract of Rhizoma coptidis (FFCERC)]. Finally, the in vivo anti-inflammatory effect and sEH inhibitory potency of FFCERC was evaluated in a lipopolysacchride (LPS)-challenged murine model of acute systemic inflammation. The inflammatory status was characterized by the inflammatory cytokines TNF-alpha and interleukin-6 (IL-6) and sEH inhibitory function was evaluated by the plasma levels of epoxyeicosantrienoic acids (EETs) and dihydroxyeicosatrienoic acids (DHETs), which are the sEH mediated substrates and products, respectively.
RESULTS: At the concentration of 25microg/mL, the crude ethanol extracts of 6 TCMs including Herba Asari, Radix Polygalae, Fructus Amomi, Radix Astragali, Radix Scutellariae, and Rhizoma Coptidis were potent against sEH. The crude extracts of Herba Asari and Rhizoma Coptidis were selected for further separation to afford FFCERC as the most promising AI for in vivo evaluation. Oral administration of FFCERC attenuated the significant increase in TNF-alpha and IL-6 caused by LPS challenge in a dose-dependent manner. In parallel, oral administration of FFCERC shifted the changes in plasma levels of EETs and DHETs caused by LPS-challenge like a synthetic sEH inhibitor.
CONCLUSIONS: A sEH inhibitory AI from Rhizoma Coptidis is anti-inflammatory and the inhibition of sEH contributes to this biological effect, indicating that sEH may be at least one of multiple therapeutic targets for relevant TCMs.
ESTHER : Liu_2016_J.Ethnopharmacol_194_475
PubMedSearch : Liu_2016_J.Ethnopharmacol_194_475
PubMedID: 27702689

Title : Occurrence and distribution of organophosphorus esters in soils and wheat plants in a plastic waste treatment area in China - Wan_2016_Environ.Pollut_214_349
Author(s) : Wan W , Zhang S , Huang H , Wu T
Ref : Environ Pollut , 214 :349 , 2016
Abstract : This study for the first time reported the occurrence, distribution and concentrations of organophosphate esters (OPEs) in soils caused by plastic waste treatment, as well as their influence on OPE accumulation in wheat (Triticum aestivum L.). Eight OPEs were detected with the total concentrations of 38-1250 ng/g dry weight in the soils from the treatment sites, and tributoxyethyl phosphate and tri(2-chloroethyl) phosphate present as the dominant OPEs. There were similar distribution patterns of OPEs and significant correlations between the total OPE concentrations in the soils from the plastic waste treatment sites with those in the nearby farmlands (P < 0.005), indicating that plastic waste treatment caused the OPE contamination of farmland soils. The uptake and translocation of OPEs by wheat were determined, with OPEs of high hydrophobicity more easily taken up from soils and OPEs with low hydrophobicity more liable to be translocated acropetally.
ESTHER : Wan_2016_Environ.Pollut_214_349
PubMedSearch : Wan_2016_Environ.Pollut_214_349
PubMedID: 27107259

Title : Covalent docking predicts substrates for haloalkanoate dehalogenase superfamily phosphatases - London_2015_Biochemistry_54_528
Author(s) : London N , Farelli JD , Brown SD , Liu C , Huang H , Korczynska M , Al-Obaidi NF , Babbitt PC , Almo SC , Allen KN , Shoichet BK
Ref : Biochemistry , 54 :528 , 2015
Abstract : Enzyme function prediction remains an important open problem. Though structure-based modeling, such as metabolite docking, can identify substrates of some enzymes, it is ill-suited to reactions that progress through a covalent intermediate. Here we investigated the ability of covalent docking to identify substrates that pass through such a covalent intermediate, focusing particularly on the haloalkanoate dehalogenase superfamily. In retrospective assessments, covalent docking recapitulated substrate binding modes of known cocrystal structures and identified experimental substrates from a set of putative phosphorylated metabolites. In comparison, noncovalent docking of high-energy intermediates yielded nonproductive poses. In prospective predictions against seven enzymes, a substrate was identified for five. For one of those cases, a covalent docking prediction, confirmed by empirical screening, and combined with genomic context analysis, suggested the identity of the enzyme that catalyzes the orphan phosphatase reaction in the riboflavin biosynthetic pathway of Bacteroides.
ESTHER : London_2015_Biochemistry_54_528
PubMedSearch : London_2015_Biochemistry_54_528
PubMedID: 25513739

Title : A novel cephalosporin deacetylating acetyl xylan esterase from Bacillus subtilis with high activity toward cephalosporin C and 7-aminocephalosporanic acid - Tian_2014_Appl.Microbiol.Biotechnol_98_2081
Author(s) : Tian Q , Song P , Jiang L , Li S , Huang H
Ref : Applied Microbiology & Biotechnology , 98 :2081 , 2014
Abstract : A cephalosporin deacetylating acetyl xylan esterase was cloned from the genomic DNA of Bacillus subtilis CICC 20034 and functionally expressed in Escherichia coli. Its gene contained an open reading frame of 957 bp encoding 318 amino acids with a calculated mass of 35,607 Da, and it displayed significant identity to acetyl xylan esterases from Bacillus sp. 916, B. subtilis 168, and Bacillus pumilus Cect5072. The enzyme was a native homohexamer but a trimer under the condition of 1% sodium dodecyl sulfate (SDS); both forms were active and could transit to each other by incubating in or removing SDS. The enzyme belongs to carbohydrate esterase family 7 and had a double specificity on both the acetylated oligosaccharide and cephalosporin C (CPC) and 7-aminocephalosporanic acid (7-ACA). The activity of this purified enzyme toward CPC and 7-ACA was highest among all the acetyl xylan esterase from CE family 7, which were 484 and 888 U/mg, respectively, and endowed itself with great industrial interest on semi-synthetic beta-lactam antibiotics. The optimum pH of the purified enzyme was 8.0, and the optimum temperature was 50 degrees C, and the enzyme had high thermal stability, broad range of pH tolerance, and extremely organic solvent tolerance.
ESTHER : Tian_2014_Appl.Microbiol.Biotechnol_98_2081
PubMedSearch : Tian_2014_Appl.Microbiol.Biotechnol_98_2081
PubMedID: 23828600

Title : Deletion of soluble epoxide hydrolase attenuates cardiac hypertrophy via down-regulation of cardiac fibroblasts-derived fibroblast growth factor-2 - Zhang_2014_Crit.Care.Med_42_e345
Author(s) : Zhang H , Wang T , Zhang K , Liu Y , Huang F , Zhu X , Wang MH , Tang W , Wang J , Huang H
Ref : Critical Care Medicine , 42 :e345 , 2014
Abstract : OBJECTIVE: Inhibition of soluble epoxide hydrolase (Ephx2) has been shown to play a protective role in cardiac hypertrophy, but the mechanism is not fully understood. We tested the hypothesis that deletion of soluble epoxide hydrolase attenuates cardiac hypertrophy via down-regulation of cardiac fibroblasts-derived fibroblast growth factor-2. DESIGN: Prospective, controlled, and randomized animal study. SETTING: University laboratory. SUBJECTS: Male wild-type C57BL/6 mice and Ephx2 (-/-) mice. INTERVENTIONS: Male wild-type or Ephx2 (-/-) mice were subjected to transverse aorta constriction surgery. MEASUREMENTS AND MAIN
RESULTS: Four weeks after transverse aorta constriction, Ephx2 (-/-) mice did not develop significant cardiac hypertrophy as that of wild-type mice, indicated by no changes in the ratio of heart weight/body weight and ventricular wall thickness after transverse aorta constriction. Cardiac fibroblast growth factor-2 increased in wild-type-transverse aorta constriction group but this did not change in Ephx2 (-/-)-transverse aorta constriction group, and the serum level of fibroblast growth factor-2 did not change in both groups. In vitro, cardiac fibroblasts were stimulated by angiotensin II to analyze the expression of fibroblast growth factor-2. The effect of increased fibroblast growth factor-2 from cardiac fibroblasts induced by angiotensin II was attenuated by soluble epoxide hydrolase deletion. ERK1/2, p38, and AKT kinase were involved in fibroblast growth factor-2 expression regulated by angiotensin II, and soluble epoxide hydrolase deletion lowered the phosphorylation of ERK1/2 not p38 or AKT to mediate fibroblast growth factor-2 expression. In addition, soluble epoxide hydrolase deletion did not attenuate cardiomyocytes hypertrophy induced by exogenous fibroblast growth factor-2.
CONCLUSIONS: Our present data demonstrated that deletion of soluble epoxide hydrolase prevented cardiac hypertrophy not only directly to cardiomyocytes but also to cardiac fibroblasts by reducing expression of fibroblast growth factor-2.
ESTHER : Zhang_2014_Crit.Care.Med_42_e345
PubMedSearch : Zhang_2014_Crit.Care.Med_42_e345
PubMedID: 24448199

Title : Draft Genome Sequence of Xylella fastidiosa Pear Leaf Scorch Strain in Taiwan - Su_2014_Genome.Announc_2_e00166
Author(s) : Su CC , Deng WL , Jan FJ , Chang CJ , Huang H , Chen J
Ref : Genome Announc , 2 : , 2014
Abstract : The draft genome sequence of Xylella fastidiosa pear leaf scorch strain PLS229, isolated from the pear cultivar Hengshan (Pyrus pyrifolia) in Taiwan, is reported here. The bacterium has a genome size of 2,733,013 bp, with a G+C content of 53.1%. The PLS229 genome was annotated and has 3,259 open reading frames and 50 RNA genes.
ESTHER : Su_2014_Genome.Announc_2_e00166
PubMedSearch : Su_2014_Genome.Announc_2_e00166
PubMedID: 24652975
Gene_locus related to this paper: xylfs-z9jn15 , 9gamm-z9jk30 , 9gamm-z9jmt7

Title : Draft Genome Sequence of Xylella fastidiosa subsp. multiplex Strain Griffin-1 from Quercus rubra in Georgia - Chen_2013_Genome.Announc_1_e00756
Author(s) : Chen J , Huang H , Chang CJ , Stenger DC
Ref : Genome Announc , 1 :e00756 , 2013
Abstract : The draft genome sequence of Xylella fastidiosa subsp. multiplex strain Griffin-1, isolated from a red oak tree (Quercus rubra) in Georgia, is reported here. The bacterium has a genome size of 2,387,314 bp, with a G+C content of 51.7%. The Griffin-1 strain genome contains 2,903 predicted open reading frames and 50 RNA genes.
ESTHER : Chen_2013_Genome.Announc_1_e00756
PubMedSearch : Chen_2013_Genome.Announc_1_e00756
PubMedID: 24115539
Gene_locus related to this paper: xylfa-pip

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 : Type II thioesterase gene (ECO-orf27) from Amycolatopsis orientalis influences production of the polyketide antibiotic, ECO-0501 (LW01) - Shen_2012_Biotechnol.Lett_34_2087
Author(s) : Shen Y , Huang H , Zhu L , Luo M , Chen D
Ref : Biotechnol Lett , 34 :2087 , 2012
Abstract : ECO-orf27 associated with the cluster of ECO-0501 (LW01) from Amycolatopsis orientalis is deduced to encode a type II thioesterase. Disruption of ECO-orf27 reduced LW01 production by 95 %. Complementation of the disrupted mutant with intact ECO-orf27 restored the production of LW01 suggesting that ECO-orf27 is crucial for LW01 biosynthesis. ECO-TE I, the gene encoding type I thioesterase from LW01 polyketide synthases, cannot complement ECO-orf27 deficient mutant distinguishing ECO-orf27 from type I thioesterase gene. Type II thioesterase gene pikAV from Streptomyces venezuelae could complement ECO-orf27 in A. orientalis indicating that the two genes are equivalent in their function. Overexpression of ECO-orf27 resulted in a 20 % increase in LW01 production providing an alternative approach for yield improvement.
ESTHER : Shen_2012_Biotechnol.Lett_34_2087
PubMedSearch : Shen_2012_Biotechnol.Lett_34_2087
PubMedID: 22850790

Title : Cloning and characterization of the biosynthetic gene cluster of the bacterial RNA polymerase inhibitor tirandamycin from marine-derived Streptomyces sp. SCSIO1666 - Mo_2011_Biochem.Biophys.Res.Commun_406_341
Author(s) : Mo X , Wang Z , Wang B , Ma J , Huang H , Tian X , Zhang S , Zhang C , Ju J
Ref : Biochemical & Biophysical Research Communications , 406 :341 , 2011
Abstract : Tirandamycins are bacterial RNA polymerase inhibitors holding great potential for antibacterial agent design. To elucidate the biosynthetic machinery and generate new derivatives, the tirandamycin biosynthetic gene cluster was cloned and sequenced from marine-derived Streptomyces sp. SCSIO1666. The biosynthetic gene cluster of tirandamycin spans a DNA region of ~56kb and consists of 15 open reading frames (ORFs) which encode three type I polyketide synthases (TrdAI, AII, AIII), one non-ribosomal peptide synthetase (TrdD), one phosphopantetheinyl transferase (TrdM), one Type II thioesterase (TrdB), one FAD-dependent oxidoreductase (TrdL), one cytochrome P450 monooxygenase (TrdI), three proteins related to resistance and regulations (TrdHJK), and four proteins with unknown function (TrdCEFG). To investigate the roles of the genes played in the biosynthetic machinery, seven genes (trdAI and trdBDFHIK) were inactivated via in frame replacement with an apramycin gene cassette using -RED recombination technology. The trdAI and trdD mutants targeting the ketosynthase and adenylation domain of TrdAI and TrdD, respectively, abolished the production of tirandamycins, confirming their involvement in the tirandamycin biosynthesis. TrdH showed high homology to LuxR family transcriptional regulatory proteins, disruption of which abolished the production of tirandamycins, indicating that TrdH is a positive regulator for tirandamycin biosynthesis. On the other hand, TrdK showed high homology to TetR-family transcriptional regulatory proteins, disruption of which significantly increased the yields of tirandamycins almost one-fold, implicating that TrdK is a negative regulator for tirandamycin biosynthesis. Disruption of the gene trdI resulted in the accumulation of the intermediate tirandamycin C (3) and a trace amount of new product tirandamycin C2 (5). A model of tirandamycin biosynthesis was proposed based on bioinformatics analyses, gene inactivation experiments and intermediates isolated from the mutants. These findings set the stage for further study of the tirandamycin biosynthetic mechanism and rationally engineer new tirandamycin analogues.
ESTHER : Mo_2011_Biochem.Biophys.Res.Commun_406_341
PubMedSearch : Mo_2011_Biochem.Biophys.Res.Commun_406_341
PubMedID: 21329667
Gene_locus related to this paper: 9actn-f1di35

Title : Complete genome sequence of Aeromonas veronii strain B565 - Li_2011_J.Bacteriol_193_3389
Author(s) : Li Y , Liu Y , Zhou Z , Huang H , Ren Y , Zhang Y , Li G , Wang L
Ref : Journal of Bacteriology , 193 :3389 , 2011
Abstract : Aeromonas veronii strain B565 was isolated from aquaculture pond sediment in China. We present here the complete genome sequence of B565 and compare it with 2 published genome sequences of pathogenic strains in the Aeromonas genus. The result represents an independent stepwise acquisition of virulence factors of pathogenic strains in this genus.
ESTHER : Li_2011_J.Bacteriol_193_3389
PubMedSearch : Li_2011_J.Bacteriol_193_3389
PubMedID: 21551296
Gene_locus related to this paper: aervb-f4d864 , aervb-f4d9b7 , 9gamm-u1fsk6 , aervb-f4dgq1

Title : Genome sequence of Acinetobacter baumannii MDR-TJ - Gao_2011_J.Bacteriol_193_2365
Author(s) : Gao F , Wang Y , Liu YJ , Wu XM , Lv X , Gan YR , Song SD , Huang H
Ref : Journal of Bacteriology , 193 :2365 , 2011
Abstract : Acinetobacter baumannii is a pathogenic species of bacteria, identified as an aerobic gram-negative bacterium, that is resistant to most antibiotics. In this study, the MDR-TJ strain was isolated at the Second Hospital of Tianjin Medical University, China, and was found to be resistant to penicillin, cephalosporins, aminoglycosides, quinolones, and also imipenem. The genome sequence of Acinetobacter baumannii strain MDR-TJ was determined by using a combination of 454 pyrosequencing and paired-end sequencing performed with the Roche Genome Sequencer FLX system to generate a scaffolded assembly.
ESTHER : Gao_2011_J.Bacteriol_193_2365
PubMedSearch : Gao_2011_J.Bacteriol_193_2365
PubMedID: 21398552
Gene_locus related to this paper: aciba-f5iht4 , aciba-a0a009wzt4

Title : Azaphilones and p-terphenyls from the mangrove endophytic fungus Penicillium chermesinum (ZH4-E2) isolated from the South China Sea - Huang_2011_J.Nat.Prod_74_997
Author(s) : Huang H , Feng X , Xiao Z , Liu L , Li H , Ma L , Lu Y , Ju J , She Z , Lin Y
Ref : Journal of Natural Products , 74 :997 , 2011
Abstract : Eight secondary metabolites, including three new azaphilones (chermesinones A-C, 1-3), three new p-terphenyls (6'-O-desmethylterphenyllin, 4; 3-hydroxy-6'-O-desmethylterphenyllin, 5; 3''-deoxy-6'-O-desmethylcandidusin B, 7), and two known p-terphenyls (6, 8), were isolated from the culture of the mangrove endophytic fungus Penicillium chermesinum (ZH4-E2). Their structures were established by spectroscopic analysis. The absolute configuration of 1 was determined by X-ray crystallography. Terphenyls 4, 5, and 6 exhibited strong inhibitory effects against alpha-glucosidase with IC50 values of 0.9, 4.9, and 2.5 muM, respectively. Terphenyls 7 and 8 showed inhibitory activity toward acetylcholinesterase with IC50 values of 7.8 and 5.2 muM.
ESTHER : Huang_2011_J.Nat.Prod_74_997
PubMedSearch : Huang_2011_J.Nat.Prod_74_997
PubMedID: 21510637

Title : Superoxide dismutase, catalase and acetylcholinesterase: biomarkers for the joint effects of cadmium, zinc and methyl parathion contamination in water - Ling_2011_Environ.Technol_32_1463
Author(s) : Ling X , Zhang Y , Lu Y , Huang H
Ref : Environ Technol , 32 :1463 , 2011
Abstract : Heavy metals are known to reduce the activities of antioxidant enzymes (e.g. superoxide dismutase, catalase), while organophosphorous insecticides are known to inhibit the activity of the enzyme acetylcholinesterase. In this study, the activities of these three enzymes in zebrafish (Danio rerio) tissues were assessed to evaluate the consequences heavy metal and organophosphate contamination in aquatic systems. When the fish were contacted with water containing a single pollutant, superoxide dismutase activity was affected by the presence of Cd but not by methyl parathion or Zn. However, catalase and acetylcholinesterase activities were sensitive to all three pollutants. The combined treatment showed that the three enzymes could be chosen as biomarkers of joint pollution by both metals and organophosphate. Toxicity tests showed an antagonism interaction between methyl parathion and Cd or Zn, and the change of enzyme activities at 96 hours was in accordance with that.
ESTHER : Ling_2011_Environ.Technol_32_1463
PubMedSearch : Ling_2011_Environ.Technol_32_1463
PubMedID: 22329136

Title : Function of phenylalanine 259 and threonine 314 within the substrate binding pocket of the juvenile hormone esterase of Manduca sexta - Kamita_2010_Biochemistry_49_3733
Author(s) : Kamita SG , Wogulis MD , Law CS , Morisseau C , Tanaka H , Huang H , Wilson DK , Hammock BD
Ref : Biochemistry , 49 :3733 , 2010
Abstract : Juvenile hormone (JH) is a key insect developmental hormone that is found at low nanomolar levels in larval insects. The methyl ester of JH is hydrolyzed in many insects by an esterase that shows high specificity for JH. We have previously determined a crystal structure of the JH esterase (JHE) of the tobacco hornworm Manduca sexta (MsJHE) [Wogulis, M., Wheelock, C. E., Kamita, S. G., Hinton, A. C., Whetstone, P. A., Hammock, B. D., and Wilson, D. K. (2006) Biochemistry 45, 4045-4057]. Our molecular modeling indicates that JH fits very tightly within the substrate binding pocket of MsJHE. This tight fit places two noncatalytic amino acid residues, Phe-259 and Thr-314, within the appropriate distance and geometry to potentially interact with the alpha,beta-unsaturated ester and epoxide, respectively, of JH. These residues are highly conserved in numerous biologically active JHEs. Kinetic analyses of mutants of Phe-259 or Thr-314 indicate that these residues contribute to the low K(M) that MsJHE shows for JH. This low K(M), however, comes at the cost of reduced substrate turnover. Neither nucleophilic attack of the resonance-stabilized ester by the catalytic serine nor the availability of a water molecule for attack of the acyl-enzyme intermediate appears to be a rate-determining step in the hydrolysis of JH by MsJHE. We hypothesize that the release of the JH acid metabolite from the substrate binding pocket limits the catalytic cycle. Our findings also demonstrate that chemical bond strength does not necessarily correlate with how reactive the bond will be to metabolism.
ESTHER : Kamita_2010_Biochemistry_49_3733
PubMedSearch : Kamita_2010_Biochemistry_49_3733
PubMedID: 20307057

Title : Development of axonal pathways in the human fetal fronto-limbic brain: histochemical characterization and diffusion tensor imaging - Vasung_2010_J.Anat_217_400
Author(s) : Vasung L , Huang H , Jovanov-Milosevic N , Pletikos M , Mori S , Kostovic I
Ref : Journal of Anatomy , 217 :400 , 2010
Abstract : The development of cortical axonal pathways in the human brain begins during the transition between the embryonic and fetal period, happens in a series of sequential events, and leads to the establishment of major long trajectories by the neonatal period. We have correlated histochemical markers (acetylcholinesterase (AChE) histochemistry, antibody against synaptic protein SNAP-25 (SNAP-25-immunoreactivity) and neurofilament 200) with the diffusion tensor imaging (DTI) database in order to make a reconstruction of the origin, growth pattern and termination of the pathways in the period between 8 and 34 postconceptual weeks (PCW). Histological sections revealed that the initial outgrowth and formation of joined trajectories of subcortico-frontal pathways (external capsule, cerebral stalk-internal capsule) and limbic bundles (fornix, stria terminalis, amygdaloid radiation) occur by 10 PCW. As early as 11 PCW, major afferent fibers invade the corticostriatal junction. At 13-14 PCW, axonal pathways from the thalamus and basal forebrain approach the deep moiety of the cortical plate, causing the first lamination. The period between 15 and 18 PCW is dominated by elaboration of the periventricular crossroads, sagittal strata and spread of fibers in the subplate and marginal zone. Tracing of fibers in the subplate with DTI is unsuccessful due to the isotropy of this zone. Penetration of the cortical plate occurs after 24-26 PCW. In conclusion, frontal axonal pathways form the periventricular crossroads, sagittal strata and 'waiting' compartments during the path-finding and penetration of the cortical plate. Histochemistry is advantageous in the demonstration of a growth pattern, whereas DTI is unique for demonstrating axonal trajectories. The complexity of fibers is the biological substrate of selective vulnerability of the fetal white matter.
ESTHER : Vasung_2010_J.Anat_217_400
PubMedSearch : Vasung_2010_J.Anat_217_400
PubMedID: 20609031

Title : A new screening method based on yeast-expressed human dipeptidyl peptidase IV and discovery of novel inhibitors - Hu_2009_Biotechnol.Lett_31_979
Author(s) : Hu CX , Huang H , Zhang L , Huang Y , Shen ZF , Cheng KD , Du GH , Zhu P
Ref : Biotechnol Lett , 31 :979 , 2009
Abstract : Dipeptidyl peptidase (DPP) IV inhibitors provide a new strategy for the treatment of type 2 diabetes. Human DPP-IV gene was cloned from differentiated Caco-2 cells and expressed in Pichia pastoris. The recombinant enzyme was used in a new system for screening of DPP-IV inhibitors. By high throughput screening, a novel compound (W5188) was identified from 75,000 compounds with an IC(50) of 6.5 microM. This method is highly reproducible and reliable for discovery of DPP-IV inhibitors as shown by Z' value of 0.73 and S/N ratio of 6.89.
ESTHER : Hu_2009_Biotechnol.Lett_31_979
PubMedSearch : Hu_2009_Biotechnol.Lett_31_979
PubMedID: 19267232

Title : Catalysis by Glomerella cingulata cutinase requires conformational cycling between the active and inactive states of its catalytic triad - Nyon_2009_J.Mol.Biol_385_226
Author(s) : Nyon MP , Rice DW , Berrisford JM , Hounslow AM , Moir AJ , Huang H , Nathan S , Mahadi NM , Bakar FD , Craven CJ
Ref : Journal of Molecular Biology , 385 :226 , 2009
Abstract : Cutinase belongs to a group of enzymes that catalyze the hydrolysis of esters and triglycerides. Structural studies on the enzyme from Fusarium solani have revealed the presence of a classic catalytic triad that has been implicated in the enzyme's mechanism. We have solved the crystal structure of Glomerella cingulata cutinase in the absence and in the presence of the inhibitors E600 (diethyl p-nitrophenyl phosphate) and PETFP (3-phenethylthio-1,1,1-trifluoropropan-2-one) to resolutions between 2.6 and 1.9 A. Analysis of these structures reveals that the catalytic triad (Ser136, Asp191, and His204) adopts an unusual configuration with the putative essential histidine His204 swung out of the active site into a position where it is unable to participate in catalysis, with the imidazole ring 11 A away from its expected position. Solution-state NMR experiments are consistent with the disrupted configuration of the triad observed crystallographically. H204N, a site-directed mutant, was shown to be catalytically inactive, confirming the importance of this residue in the enzyme mechanism. These findings suggest that, during its catalytic cycle, cutinase undergoes a significant conformational rearrangement converting the loop bearing the histidine from an inactive conformation, in which the histidine of the triad is solvent exposed, to an active conformation, in which the triad assumes a classic configuration.
ESTHER : Nyon_2009_J.Mol.Biol_385_226
PubMedSearch : Nyon_2009_J.Mol.Biol_385_226
PubMedID: 18983850
Gene_locus related to this paper: colgl-cutas

Title : Protein tyrosine kinase involvement in learning-produced changes in Hermissenda type B photoreceptors - Jin_2009_J.Neurophysiol_102_3573
Author(s) : Jin I , Huang H , Smith B , Farley J
Ref : Journal of Neurophysiology , 102 :3573 , 2009
Abstract : Learning-correlated changes in the excitability and photoresponses of Hermissenda's ocular type B photoreceptors are mediated by reductions in two distinct K(+) currents, I(A) and I(K-Ca). The suppression of these K(+) currents has been linked to conditioning-produced activation of protein kinase C (PKC). The question of whether PKC accounts completely for the changes in excitability and K(+) currents or whether other kinase(s) are involved has received little attention. In the present experiments, we asked whether protein tyrosine kinases (PTKs) might also contribute to conditioning-produced alterations in B cells. We found that the PTK inhibitors genistein and lavendustin A greatly reduced cumulative depolarization of type B cells, a short-term correlate of associative learning. This disruption occurred even when PKC activation had been either occluded by preexposure of type B cells to a phorbol ester or otherwise prevented by the pseudosubstrate inhibitor peptide PKC[19-31]. PTK inhibitors also increased the amplitude of the transient (I(A)) and delayed (I(Delayed)) components of voltage-dependent K(+) current that have previously been shown to be selectively reduced by conditioning and to contribute to cumulative depolarization. Genistein partially prevented the reduction of I(A) and I(Delayed) due to in vitro conditioning and blocked the changes in their voltage dependencies. Ionophoresis of pervanadate ion, a potent inhibitor of protein tyrosine phosphatases, depolarized type B photoreceptors and occluded conditioning-produced cumulative depolarization. Pervanadate also suppressed I(A) and I(Delayed), reduced their voltage dependence, and altered inactivation kinetics for I(A), mimicking conditioning. Western blot analysis using a phosphotyrosine antibody indicated that conditioning increased the phosphotyrosine content of many proteins within the Hermissenda CNS. Collectively, our results suggest that in addition to PKC, one or more PTKs play an important role in conditioning-produced changes in type B cell excitability. PTKs and PKCs converge to effect reductions in B cell K(+) currents during conditioning, apparently through distinct biophysical mechanisms.
ESTHER : Jin_2009_J.Neurophysiol_102_3573
PubMedSearch : Jin_2009_J.Neurophysiol_102_3573
PubMedID: 19812284

Title : A novel cold-adapted phospholipase A(1) from Serratia sp. xjF1: Gene cloning, expression and characterization - Fu_2008_Enzyme.Microb.Technol_42_187
Author(s) : Fu J , Huang H , Meng K , Yuan T , Yao B , Shi Y , Ouyang P
Ref : Enzyme Microb Technol , 42 :187 , 2008
Abstract : The gene encoding a cold-adapted phospholipase A(1) (PLA(1)) from a psychrotrophic, glacier soil bacterium Serratia sp. xjF1 was cloned by two-step PCR (general PCR and TAIL-PCR). The full-length fragment comprised two open reading frames plA and plS. The gene product of plA encoding 320 amino acids with a molecular weight of 33.8kDa was identified as a phospholipase A(1). Its amino acid sequence exhibited the highest homology to PLA(1) of Serratia marcescens (71%). plS encoded a protein of 251 amino acids, which showed no enzymatic activity. The result of plA expression in Escherichia coli indicated that plS might improve the efficient expression of PLA(1) in E. coli. Furthermore, PLA(1) was functionally expressed in Pichia pastoris, yielding 41.8U/mL in a 3.7L fermentor. The purified recombinant phospholipase A(1) (rPLA(1)) had features typical of cold-adapted enzymes with a temperature optimum of 35 degrees C and a maximum activity of 70% at 10 degrees C. The rate of catalysis was optimal at pH 9.0 and the enzyme could be slightly activated by Ca(2+). This is the first report on gene isolation and expression of cold-adapted PLA(1).
ESTHER : Fu_2008_Enzyme.Microb.Technol_42_187
PubMedSearch : Fu_2008_Enzyme.Microb.Technol_42_187
PubMedID: 22578870
Gene_locus related to this paper: 9entr-a9x3m0

Title : Crystallization and preliminary X-ray analysis of recombinant Glomerella cingulata cutinase - Nyon_2008_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_64_504
Author(s) : Nyon MP , Rice DW , Berrisford JM , Huang H , Moir AJ , Craven CJ , Nathan S , Mahadi NM , Abu Bakar FD
Ref : Acta Crystallographica Sect F Struct Biol Cryst Commun , 64 :504 , 2008
Abstract : Cutinase catalyzes the hydrolysis of water-soluble esters and long-chain triglycerides and belongs to the family of serine hydrolases. The enzyme is thought to represent an evolutionary link between the esterase and lipase families and has potential applications in a wide range of industrial hydrolytic processes, for which an understanding of the molecular basis of its substrate specificity is critical. Glomerella cingulata cutinase has been cloned and the protein has been overexpressed in Escherichia coli, purified and subsequently crystallized in a wide range of different crystal forms in the presence and absence of inhibitors. The best crystals are those of the apo cutinase, which diffract to beyond 1.6 A resolution and belong to space group P4(1)2(1)2 or P4(3)2(1)2. Crystals of cutinase with the inhibitors PETFP or E600 belong to space groups P2(1)2(1)2(1) and P2(1), respectively, and diffract to approximately 2.5 A resolution. All of the crystals are suitable for structural studies, which are currently ongoing.
ESTHER : Nyon_2008_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_64_504
PubMedSearch : Nyon_2008_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_64_504
PubMedID: 18540061
Gene_locus related to this paper: colgl-cutas

Title : Pharmacological profile of PMS777, a new AChE inhibitor with PAF antagonistic activity - Li_2007_Int.J.Neuropsychopharmacol_10_21
Author(s) : Li J , Huang H , Miezan Ezoulin JM , Gao XL , Massicot F , Dong CZ , Heymans F , Chen HZ
Ref : Int J Neuropsychopharmacol , 10 :21 , 2007
Abstract : The key pathophysiological mechanisms in Alzheimer's disease involve the selective loss of cholinergic neurons and pro-inflammatory mediator-related chronic inflammatory responses in the brain, therefore interventions of these processes are crucial to the treatment of this disease. In the present study, the pharmacological profile of PMS777, a new acetylcholinesterase (AChE) inhibitor with platelet-activating factor (PAF) antagonistic activity, has been evaluated in vitro and in vivo. PMS777 (1-100 microM) dose-dependently inhibited PAF-induced rabbit platelet aggregation by competing with [3H]PAF for its receptor on platelets, and protected a human neuroblastoma cell line SH-SY5Y against PAF-induced neurotoxicity. Moreover, it markedly inhibited brain AChE activity in mice and showed a modest selectivity for AChE (AChE: IC50=2.48+/-0.12 microM; butyrylcholinesterase: IC50=4.47+/-0.15 microM). Ex vivo, PMS777 (5, 10, 20 or 40 mg/kg i.p.) reduced brain AChE activity in a dose-dependent manner. In-vivo studies revealed that PMS777 (0.25, 0.5, 1, 2.5 or 5 mg/kg i.p.) could reverse scopolamine-induced memory retrieval deficits in mice, and displayed a typical bell-shaped dose-response relationship. Taken together, these results demonstrate that PMS777 possesses dual activities for PAF receptor antagonism and AChE inhibition, suggesting that this compound may be a promising lead compound for further investigation related to the treatment for Alzheimer's disease.
ESTHER : Li_2007_Int.J.Neuropsychopharmacol_10_21
PubMedSearch : Li_2007_Int.J.Neuropsychopharmacol_10_21
PubMedID: 16426477

Title : Evaluation of chiral alpha-cyanoesters as general fluorescent substrates for screening enantioselective esterases - Huang_2006_J.Agric.Food.Chem_54_694
Author(s) : Huang H , Nishi K , Gee SJ , Hammock BD
Ref : Journal of Agricultural and Food Chemistry , 54 :694 , 2006
Abstract : Esterases play a crucial role in industrial chemical synthesis, maintaining normal physiological metabolism and detoxifying exogenous ester-containing toxicants. To meet the rapidly increasing industrial need for all kinds of esterases, especially enantioselective esterases used to generate highly pure chiral compounds, general substrates are necessary for rapid screening, monitoring, purification, and characterization. In this study, general fluorescent substrates including phenolic derivatives and alpha-cyanoesters were evaluated for sensitivity in detecting esterases in buffer systems. Results with two different esterases and different incubation times suggested that the alpha-cyanoesters examined were significantly more sensitive at detecting esterases than the corresponding tested phenolic derivatives. More importantly, alpha-cyanoesters, containing a secondary alcohol, possess at least one chiral center; thus, they are tools to screen for enantioselective hydrolysis. Results indicated that the enantioselectivity of esterases toward general alpha-cyanoesters strongly depended on the esterase and the substrate, but the majority of esterases examined preferred S-isomers to their corresponding R-enantiomers. Most appealing was the very high enantioselectivity displayed in cytosolic esterases of the house fly. The potential utility of such esterases is discussed. In addition, the use of alpha-cyanoesters as chiral fluorescent substrates was demonstrated for monitoring in enantioselective esterases.
ESTHER : Huang_2006_J.Agric.Food.Chem_54_694
PubMedSearch : Huang_2006_J.Agric.Food.Chem_54_694
PubMedID: 16448170

Title : Characterization of pyrethroid hydrolysis by the human liver carboxylesterases hCE-1 and hCE-2 - Nishi_2006_Arch.Biochem.Biophys_445_115
Author(s) : Nishi K , Huang H , Kamita SG , Kim IH , Morisseau C , Hammock BD
Ref : Archives of Biochemistry & Biophysics , 445 :115 , 2006
Abstract : Carboxylesterases hydrolyze a large array of endogenous and exogenous ester-containing compounds, including pyrethroid insecticides. Herein, we report the specific activities and kinetic parameters of human carboxylesterase (hCE)-1 and hCE-2 using authentic pyrethroids and pyrethroid-like, fluorescent surrogates. Both hCE-1 and hCE-2 hydrolyzed type I and II pyrethroids with strong stereoselectivity. For example, the trans-isomers of permethrin and cypermethrin were hydrolyzed much faster than corresponding cis-counterparts by both enzymes. Kinetic values of hCE-1 and hCE-2 were determined using cypermethrin and 11 stereoisomers of the pyrethroid-like, fluorescent surrogates. K(m) values for the authentic pyrethroids and fluorescent surrogates were in general lower than those for other ester-containing substrates of hCEs. The pyrethroid-like, fluorescent surrogates were hydrolyzed at rates similar to the authentic pyrethroids by both enzymes, suggesting the potential of these compounds as tools for high throughput screening of esterases that hydrolyze pyrethroids.
ESTHER : Nishi_2006_Arch.Biochem.Biophys_445_115
PubMedSearch : Nishi_2006_Arch.Biochem.Biophys_445_115
PubMedID: 16359636
Gene_locus related to this paper: human-CES1 , human-CES2

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 : Stereoselective hydrolysis of pyrethroid-like fluorescent substrates by human and other mammalian liver carboxylesterases - Huang_2005_Chem.Res.Toxicol_18_1371
Author(s) : Huang H , Fleming CD , Nishi K , Redinbo MR , Hammock BD
Ref : Chemical Research in Toxicology , 18 :1371 , 2005
Abstract : Mammalian hepatic carboxylesterases (CEs) play important roles in the detoxification of ester-containing pyrethroids, which are widely used for the control of agricultural pests and disease vectors such as mosquitoes. Pyrethroids and pyrethroid-like fluorescent substrates exhibit a consistent pattern of stereoselective hydrolysis by a recombinant murine hepatic CE. We sought to understand whether this pattern is maintained in other hepatic CEs and to unravel the origin of the stereoselectivity. We found that all hepatic CEs tested displayed a consistent pattern of stereoselective hydrolysis: the chiral center(s) in the acid moiety more strongly influenced stereoselective hydrolysis than the chiral center in the alcohol moiety. For cypermethrin analogues with a cyclopropane ring in the acid moiety, trans-isomers were generally hydrolyzed faster than the corresponding cis-isomers. For fenvalerate analogues without a cyclopropane ring in the acid moiety, 2R-isomers were better substrates than 2S-isomers. These general hydrolytic patterns were examined by modeling the pyrethroid-like analogues within the active site of the crystal structure of human carboxylesterase 1 (hCE1). Stereoselective steric clashes were found to occur between the acid moieties and either the catalytic Ser loop (residues 219-225) or the oxyanion hole (residues140-144). These clashes appeared to explain the stereopreference between trans- and cis-isomers of cypermethrin analogues, and the 2R- and 2S-isomers of fenvalerate analogues by hCE1. The implications these findings have on the design and use of effective pesticides are discussed.
ESTHER : Huang_2005_Chem.Res.Toxicol_18_1371
PubMedSearch : Huang_2005_Chem.Res.Toxicol_18_1371
PubMedID: 16167828

Title : Individual variability in esterase activity and CYP1A levels in Chinook salmon (Oncorhynchus tshawytscha) exposed to esfenvalerate and chlorpyrifos - Wheelock_2005_Aquat.Toxicol_74_172
Author(s) : Wheelock CE , Eder KJ , Werner I , Huang H , Jones PD , Brammell BF , Elskus AA , Hammock BD
Ref : Aquat Toxicol , 74 :172 , 2005
Abstract : Acetylcholinesterase (AChE) activity has traditionally been monitored as a biomarker of organophosphate (OP) and/or carbamate exposure. However, AChE activity may not be the most sensitive endpoint for these agrochemicals, because OPs can cause adverse physiological effects at concentrations that do not affect AChE activity. Carboxylesterases are a related family of enzymes that have higher affinity than AChE for some OPs and carbamates and may be more sensitive indicators of environmental exposure to these pesticides. In this study, carboxylesterase and AChE activity, cytochrome P4501A (CYP1A) protein levels, and mortality were measured in individual juvenile Chinook salmon (Oncorhynchus tshawytscha) following exposure to an OP (chlorpyrifos) and a pyrethroid (esfenvalerate). As expected, high doses of chlorpyrifos and esfenvalerate were acutely toxic, with nominal concentrations (100 and 1 microg/l, respectively) causing 100% mortality within 96 h. Exposure to chlorpyrifos at a high dose (7.3 microg/l), but not a low dose (1.2 microg/l), significantly inhibited AChE activity in both brain and muscle tissue (85% and 92% inhibition, respectively), while esfenvalerate exposure had no effect. In contrast, liver carboxylesterase activity was significantly inhibited at both the low and high chlorpyrifos dose exposure (56% and 79% inhibition, respectively), while esfenvalerate exposure still had little effect. The inhibition of carboxylesterase activity at levels of chlorpyrifos that did not affect AChE activity suggests that some salmon carboxylesterase isozymes may be more sensitive than AChE to inhibition by OPs. CYP1A protein levels were approximately 30% suppressed by chlorpyrifos exposure at the high dose, but esfenvalerate had no effect. Three teleost species, Chinook salmon, medaka (Oryzias latipes) and Sacramento splittail (Pogonichthys macrolepidotus), were examined for their ability to hydrolyze a series of pyrethroid surrogate substrates and in all cases hydrolysis activity was undetectable. Together these data suggest that (1) carboxylesterase activity inhibition may be a more sensitive biomarker for OP exposure than AChE activity, (2) neither AChE nor carboxylesterase activity are biomarkers for pyrethroid exposure, (3) CYP1A protein is not a sensitive marker for these agrochemicals and (4) slow hydrolysis rates may be partly responsible for acute pyrethroid toxicity in fish.
ESTHER : Wheelock_2005_Aquat.Toxicol_74_172
PubMedSearch : Wheelock_2005_Aquat.Toxicol_74_172
PubMedID: 16011852

Title : Identification, expression, and purification of a pyrethroid-hydrolyzing carboxylesterase from mouse liver microsomes - Stok_2004_J.Biol.Chem_279_29863
Author(s) : Stok JE , Huang H , Jones PD , Wheelock CE , Morisseau C , Hammock BD
Ref : Journal of Biological Chemistry , 279 :29863 , 2004
Abstract : Carboxylesterases are enzymes that catalyze the hydrolysis of a wide range of ester-containing endogenous and xenobiotic compounds. Although the use of pyrethroids is increasing, the specific enzymes involved in the hydrolysis of these insecticides have yet to be identified. A pyrethroid-hydrolyzing enzyme was partially purified from mouse liver microsomes using a fluorescent reporter similar in structure to cypermethrin (Shan, G., and Hammock, B. D. (2001) Anal. Biochem. 299, 54-62 and Wheelock, C. E., Wheelock, A. M., Zhang, R., Stok, J. E., Morisseau, C., Le Valley, S. E., Green, C. E., and Hammock, B. D. (2003) Anal. Biochem. 315, 208-222) and subsequently identified as a carboxylesterase (NCBI accession number BAC36707). The expressed sequence tag was then cloned, expressed in baculovirus, and purified to homogeneity. Kinetic constants for a large number of both type I and type II pyrethroid or pyrethroid-like substrates were determined. This esterase possesses similar kinetic constants for cypermethrin and its fluorescent-surrogate (k(cat) = 0.12 +/- 0.03 versus 0.11 +/- 0.01 s(-1)). Compared with their cis- counterparts, trans-permethrin and cypermethrin were hydrolyzed 22- and 4-fold faster, respectively. Of the four fenvalerate isomers the (2R)(alphaR)-isomer was hydrolyzed at least 1 order of magnitude faster than any other isomer. However, it is unlikely that this enzyme accounts for the total pyrethroid hydrolysis in the microsomes because both isoelectrofocusing and native PAGE indicate the presence of a second region of cypermethrin-metabolizing enzymes. A second carboxylesterase gene (NCBI accession number NM_133960), isolated during a cDNA mouse liver library screening, was also found to hydrolyze pyrethroids. Both these enzymes could be used as preliminary tools in establishing the relative toxicity of new pyrethroids.
ESTHER : Stok_2004_J.Biol.Chem_279_29863
PubMedSearch : Stok_2004_J.Biol.Chem_279_29863
PubMedID: 15123619
Gene_locus related to this paper: mouse-Ces2a , mouse-Ces2e

Title : Genome sequence of the Brown Norway rat yields insights into mammalian evolution - Gibbs_2004_Nature_428_493
Author(s) : Gibbs RA , Weinstock GM , Metzker ML , Muzny DM , Sodergren EJ , Scherer S , Scott G , Steffen D , Worley KC , Burch PE , Okwuonu G , Hines S , Lewis L , DeRamo C , Delgado O , Dugan-Rocha S , Miner G , Morgan M , Hawes A , Gill R , Celera , Holt RA , Adams MD , Amanatides PG , Baden-Tillson H , Barnstead M , Chin S , Evans CA , Ferriera S , Fosler C , Glodek A , Gu Z , Jennings D , Kraft CL , Nguyen T , Pfannkoch CM , Sitter C , Sutton GG , Venter JC , Woodage T , Smith D , Lee HM , Gustafson E , Cahill P , Kana A , Doucette-Stamm L , Weinstock K , Fechtel K , Weiss RB , Dunn DM , Green ED , Blakesley RW , Bouffard GG , de Jong PJ , Osoegawa K , Zhu B , Marra M , Schein J , Bosdet I , Fjell C , Jones S , Krzywinski M , Mathewson C , Siddiqui A , Wye N , McPherson J , Zhao S , Fraser CM , Shetty J , Shatsman S , Geer K , Chen Y , Abramzon S , Nierman WC , Havlak PH , Chen R , Durbin KJ , Egan A , Ren Y , Song XZ , Li B , Liu Y , Qin X , Cawley S , Cooney AJ , D'Souza LM , Martin K , Wu JQ , Gonzalez-Garay ML , Jackson AR , Kalafus KJ , McLeod MP , Milosavljevic A , Virk D , Volkov A , Wheeler DA , Zhang Z , Bailey JA , Eichler EE , Tuzun E , Birney E , Mongin E , Ureta-Vidal A , Woodwark C , Zdobnov E , Bork P , Suyama M , Torrents D , Alexandersson M , Trask BJ , Young JM , Huang H , Wang H , Xing H , Daniels S , Gietzen D , Schmidt J , Stevens K , Vitt U , Wingrove J , Camara F , Mar Alba M , Abril JF , Guigo R , Smit A , Dubchak I , Rubin EM , Couronne O , Poliakov A , Hubner N , Ganten D , Goesele C , Hummel O , Kreitler T , Lee YA , Monti J , Schulz H , Zimdahl H , Himmelbauer H , Lehrach H , Jacob HJ , Bromberg S , Gullings-Handley J , Jensen-Seaman MI , Kwitek AE , Lazar J , Pasko D , Tonellato PJ , Twigger S , Ponting CP , Duarte JM , Rice S , Goodstadt L , Beatson SA , Emes RD , Winter EE , Webber C , Brandt P , Nyakatura G , Adetobi M , Chiaromonte F , Elnitski L , Eswara P , Hardison RC , Hou M , Kolbe D , Makova K , Miller W , Nekrutenko A , Riemer C , Schwartz S , Taylor J , Yang S , Zhang Y , Lindpaintner K , Andrews TD , Caccamo M , Clamp M , Clarke L , Curwen V , Durbin R , Eyras E , Searle SM , Cooper GM , Batzoglou S , Brudno M , Sidow A , Stone EA , Payseur BA , Bourque G , Lopez-Otin C , Puente XS , Chakrabarti K , Chatterji S , Dewey C , Pachter L , Bray N , Yap VB , Caspi A , Tesler G , Pevzner PA , Haussler D , Roskin KM , Baertsch R , Clawson H , Furey TS , Hinrichs AS , Karolchik D , Kent WJ , Rosenbloom KR , Trumbower H , Weirauch M , Cooper DN , Stenson PD , Ma B , Brent M , Arumugam M , Shteynberg D , Copley RR , Taylor MS , Riethman H , Mudunuri U , Peterson J , Guyer M , Felsenfeld A , Old S , Mockrin S , Collins F
Ref : Nature , 428 :493 , 2004
Abstract : The laboratory rat (Rattus norvegicus) is an indispensable tool in experimental medicine and drug development, having made inestimable contributions to human health. We report here the genome sequence of the Brown Norway (BN) rat strain. The sequence represents a high-quality 'draft' covering over 90% of the genome. The BN rat sequence is the third complete mammalian genome to be deciphered, and three-way comparisons with the human and mouse genomes resolve details of mammalian evolution. This first comprehensive analysis includes genes and proteins and their relation to human disease, repeated sequences, comparative genome-wide studies of mammalian orthologous chromosomal regions and rearrangement breakpoints, reconstruction of ancestral karyotypes and the events leading to existing species, rates of variation, and lineage-specific and lineage-independent evolutionary events such as expansion of gene families, orthology relations and protein evolution.
ESTHER : Gibbs_2004_Nature_428_493
PubMedSearch : Gibbs_2004_Nature_428_493
PubMedID: 15057822
Gene_locus related to this paper: rat-abhea , rat-abheb , rat-cd029 , rat-d3zaw4 , rat-dpp9 , rat-d3zhq1 , rat-d3zkp8 , rat-d3zuq1 , rat-d3zxw8 , rat-d4a4w4 , rat-d4a7w1 , rat-d4a9l7 , rat-d4a071 , rat-d4aa31 , rat-d4aa33 , rat-d4aa61 , rat-dglb , rat-f1lz91 , rat-Kansl3 , rat-nceh1 , rat-Tex30 , ratno-1hlip , ratno-1neur , ratno-1plip , ratno-2neur , ratno-3neur , ratno-3plip , ratno-ABH15 , ratno-ACHE , ratno-balip , ratno-BCHE , ratno-cauxin , ratno-Ces1d , ratno-Ces1e , ratno-Ces2f , ratno-d3ze31 , ratno-d3zp14 , ratno-d3zxi3 , ratno-d3zxq0 , ratno-d3zxq1 , ratno-d4a3d4 , ratno-d4aa05 , ratno-dpp4 , ratno-dpp6 , ratno-est8 , ratno-FAP , ratno-hyep , ratno-hyes , ratno-kmcxe , ratno-lmcxe , ratno-LOC246252 , ratno-MGLL , ratno-pbcxe , ratno-phebest , ratno-Ppgb , ratno-q4qr68 , ratno-q6ayr2 , ratno-q6q629 , ratno-SPG21 , ratno-thyro , rat-m0rc77 , rat-a0a0g2k9y7 , rat-a0a0g2kb83 , rat-d3zba8 , rat-d3zbj1 , rat-d3zcr8 , rat-d3zxw5 , rat-d4a340 , rat-f1lvg7 , rat-m0r509 , rat-m0r5d4 , rat-b5den3 , rat-d3zxk4 , rat-d4a1b6 , rat-d3zmg4 , rat-ab17c

Title : Genome-wide ORFeome cloning and analysis of Arabidopsis transcription factor genes - Gong_2004_Plant.Physiol_135_773
Author(s) : Gong W , Shen YP , Ma LG , Pan Y , Du YL , Wang DH , Yang JY , Hu LD , Liu XF , Dong CX , Ma L , Chen YH , Yang XY , Gao Y , Zhu D , Tan X , Mu JY , Zhang DB , Liu YL , Dinesh-Kumar SP , Li Y , Wang XP , Gu HY , Qu LJ , Bai SN , Lu YT , Li JY , Zhao JD , Zuo J , Huang H , Deng XW , Zhu YX
Ref : Plant Physiol , 135 :773 , 2004
Abstract : Here, we report our effort in generating an ORFeome collection for the Arabidopsis transcription factor (TF) genes. In total, ORFeome clones representing 1,282 Arabidopsis TF genes have been obtained in the Gateway high throughput cloning pENTR vector, including 411 genes whose annotation lack cDNA support. All the ORFeome inserts have also been mobilized into a yeast expression destination vector, with an estimated 85% rate of expressing the respective proteins. Sequence analysis of these clones revealed that 34 of them did not match with either the reported cDNAs or current predicted open-reading-frame sequences. Among those, novel alternative splicing of TF gene transcripts is responsible for the observed differences in at least five genes. However, those alternative splicing events do not appear to be differentially regulated among distinct Arabidopsis tissues examined. Lastly, expression of those TF genes in 17 distinct Arabidopsis organ types and the cultured cells was profiled using a 70-mer oligo microarray.
ESTHER : Gong_2004_Plant.Physiol_135_773
PubMedSearch : Gong_2004_Plant.Physiol_135_773
PubMedID: 15208423
Gene_locus related to this paper: arath-Q9FN74

Title : Epoxide hydrolase-catalyzed enantioselective synthesis of chiral 1,2-diols via desymmetrization of meso-epoxides. -
Author(s) : Zhao L , Han B , Huang Z , Miller M , Huang H , Malashock DS , Zhu Z , Milan A , Robertson DE , Weiner DP , Burk MJ
Ref : J Am Chem Soc , 126 :11156 , 2004
PubMedID: 15355089

Title : Chemosensory conditioning in molluscs: II. A critical review - Farley_2004_Learn.Behav_32_277
Author(s) : Farley J , Jin I , Huang H , Kim JI
Ref : Learn Behav , 32 :277 , 2004
Abstract : We critically review chemosensory conditioning studies with molluscs and find that, in many studies, the influence of nonassociative processes complicates, obscures, and renders ambiguous the unique contribution of associative learning. These nonassociative processes include sensory adaptation, habituation, sensitization, and changes in feeding motivation. They arise from both the food extracts that have often been used as conditioned stimuli and the aversive stimuli that have been used as unconditioned stimuli.
ESTHER : Farley_2004_Learn.Behav_32_277
PubMedSearch : Farley_2004_Learn.Behav_32_277
PubMedID: 15672823

Title : Chemosensory conditioning in molluscs: I. Failure of contextual conditioning in Hermissenda - Jin_2004_Learn.Behav_32_257
Author(s) : Jin I , Huang H , Kim JI , Farley J
Ref : Learn Behav , 32 :257 , 2004
Abstract : Aversive chemosensory conditioning alters Hermissenda's feeding behavior. But opposite behavioral changes have been reported, depending on whether discrete-trial or context-conditioning paradigms were used, raising questions about the roles of associative and nonassociative processes. We attempted to produce chemosensory contextual conditioning but failed to do so across a wide range of conditions. In Experiments 1-3, we observed large, nonspecific bite latency increases to shellfish extracts, regardless of whether they had signaled the presence or absence of shaking. In Experiment 4, we found that mere exposure to shellfish extract produced latency increases; vestibular stimulation was unnecessary. In a final experiment, using Y-maze choice tests, we failed to observe selective reductions in animals' preference for shellfish paired with shaking. Nonassociative processes stemming from prolonged exposure to concentrated shellfish extracts appear to be major factors in our failure to demonstrate associative chemosensory contextual conditioning.
ESTHER : Jin_2004_Learn.Behav_32_257
PubMedSearch : Jin_2004_Learn.Behav_32_257
PubMedID: 15672822

Title : Multiple reactive immunization towards the hydrolysis of organophosphorus nerve agents: hapten design and synthesis - Huang_2001_Bioorg.Med.Chem_9_3185
Author(s) : Huang H , Han WG , Noodleman L , Grynszpan F
Ref : Bioorganic & Medicinal Chemistry , 9 :3185 , 2001
Abstract : We designed and synthesized a series of haptens to elicit catalytic antibodies with phosphatase activity against nerve agents. The design is based on the novel concept of multiple reactive immunization which aims to afford two or more catalytic residues within the antibody's binding cleft. The haptens showed the desired reactivity in vitro and were submitted for immunization.
ESTHER : Huang_2001_Bioorg.Med.Chem_9_3185
PubMedSearch : Huang_2001_Bioorg.Med.Chem_9_3185
PubMedID: 11711294

Title : Carboxypeptidase A3 (CPA3): a novel gene highly induced by histone deacetylase inhibitors during differentiation of prostate epithelial cancer cells - Huang_1999_Cancer.Res_59_2981
Author(s) : Huang H , Reed CP , Zhang JS , Shridhar V , Wang L and
Ref : Cancer Research , 59 :2981 , 1999
Abstract : Butyrate and its structural analogues have recently entered clinical trials as a potential drug for differentiation therapy of advanced prostate cancer. To better understand the molecular mechanism(s) involved in prostate cancer differentiation, we used mRNA differential display to identify the gene(s) induced by butyrate. We found that the androgen-independent prostate cancer cell line PC-3 undergoes terminal differentiation and apoptosis after treatment with sodium butyrate (NaBu). A novel cDNA designated carboxypeptidase A3 (CPA3), which was up-regulated in NaBu-treated PC-3 cells, was identified and characterized. This gene expresses a 2795-bp mRNA encoding a protein with an open reading frame of 421 amino acids. CPA3 has 37-63% amino acid identity with zinc CPs from different mammalian species. It also shares 27-43% amino acid similarity with zinc CPs from several nonmammalian species, including Escherichia coli, yeast, Caenorhabditis elegans, and Drosophila. The structural similarity between CPA3 and its closest homologues indicates that the putative CPA3 protein contains a 16-residue signal peptide sequence, a 95-residue NH2-terminal activation segment, and a 310-residue CP enzyme domain. The consistent induction of CPA3 by NaBu in several prostate cancer cell lines led us to investigate the signaling pathway involved in the induction of CPA3 mRNA. Trichostatin A, a potent and specific inhibitor of histone deacetylase, also induced CPA3 mRNA expression, suggesting that CPA3 gene induction is mediated by histone hyperacetylation. We demonstrated that CPA3 induction was a downstream effect of the treatment with butyrate or trichostatin A, but that the induction of p21(WAF1/CIP1) occurred immediately after these treatments. We also demonstrated that the induction of CPA3 mRNA by NaBu was inhibited by p21(WAF1/CIP1) antisense mRNA expression, indicating that p21 transactivation is required for the induction of CPA3 by NaBu. Our data demonstrate that the histone hyperacetylation signaling pathway is activated during NaBu-mediated differentiation of PC-3 cells, and the new gene, CPA3, is involved in this pathway.
ESTHER : Huang_1999_Cancer.Res_59_2981
PubMedSearch : Huang_1999_Cancer.Res_59_2981
PubMedID: 10383164

Title : Role of reactive oxygen metabolites in organophosphate-bidrin-induced renal tubular cytotoxicity - Poovala_1999_J.Am.Soc.Nephrol_10_1746
Author(s) : Poovala VS , Huang H , Salahudeen AK
Ref : J Am Soc Nephrol , 10 :1746 , 1999
Abstract : Due to low toxicity to nontarget species and rapid degradation after its application, organophosphate (OP) remains a widely used class of pesticide. Suicidal or accidental overdose of OP can result in acute tubular necrosis. Experimental evidence shows little correlation between the renal tubular necrosis and the degree of OP-induced acetylcholinesterase inhibition, the main mechanism of OP's toxicity, suggesting the involvement of alternate mechanisms. Since reactive oxygen species (ROS) are known mediators of many toxin-induced renal injuries, this study was conducted to investigate whether ROS play a role in Bidrin (BD)-induced renal tubular epithelial cell (LLC-PK1) toxicity. BD is an OP insecticide formulation with dicrotophos as the active ingredient. LLC-PK1 cell death, determined by lactate dehydrogenase (LDH) release (% of total), rose concentration- and time-dependently after exposure of the cells to 1000, 1250, 1500, 1750, and 2000 ppm of BD for 6, 12, 24, and 48 h. Antioxidants 2-methylaminochroman (2-MAC; 0.3 to 2.5 microM) and desferrioxamine (DFO; 0.25 to 2 mM) reduced cell damage induced by 1250 ppm of BD over a 24-h incubation in a concentration-related manner. The greatest reductions in % LDH were produced by DFO 2 mM and 2-MAC 2.5 microM, both significantly lower than BD alone. H2O2 levels (micromol/mg protein per h) were significantly elevated after exposure to 1250 ppm of BD. Significantly increased malondialdehyde formation (nmol/mg protein) compared with control was also found in BD-exposed cells indicating enhanced lipid peroxidation. Malondialdehyde generation was significantly suppressed by 2-MAC and DFO. These results demonstrate that the organophosphate BD can cause direct tubular cytotoxicity, and implicate, at least in part, a role for ROS and accompanying lipid peroxidation in cytotoxicity. Based on these direct in vitro findings, it is hypothesized that, besides hypotension that often accompanies OP intoxication, OP-induced oxidative stress at the tubular level may play a role in the pathogenesis of acute tubular necrosis.
ESTHER : Poovala_1999_J.Am.Soc.Nephrol_10_1746
PubMedSearch : Poovala_1999_J.Am.Soc.Nephrol_10_1746
PubMedID: 10446942

Title : Analysis of two gene regions involved in the expression of the imipenem-specific, outer membrane porin protein OprD of Pseudomonas aeruginosa - Huang_1992_FEMS.Microbiol.Lett_76_267
Author(s) : Huang H , Siehnel RJ , Bellido F , Rawling E , Hancock RE
Ref : FEMS Microbiology Letters , 76 :267 , 1992
Abstract : A Tn501 mutant of Pseudomonas aeruginosa resistant to imipenem and lacking the imipenem-specific outer membrane porin protein OprD was isolated. The mutation could be complemented to imipenem susceptibility and OprD-sufficiency by a cloned 6-kb EcoRI-PstI fragment of DNA from the region of chromosome of the wild-type strain surrounding the site of Tn501 insertion. However, this fragment did not contain the oprD structural gene as judged by its inability to hybridize with an oligonucleotide corresponding to the N-terminal amino acid sequence of OprD. DNA sequencing of 3.9 kb of the region surrounding the Tn501 insertion site revealed three large open reading frames, one of which would be interrupted by the Tn501 insertion in the mutant. This latter open reading frame, named opdE (for putative regulator of oprD expression), predicted a hydrophobic protein of M(r) 41,592. Using the above-mentioned oligonucleotide, the oprD structural gene was cloned and expressed in Escherichia coli on a 2.1-kb Bam HI-KpnI fragment. DNA sequencing predicted a 420 amino acid mature OprD protein with a 23 amino acid signal sequence.
ESTHER : Huang_1992_FEMS.Microbiol.Lett_76_267
PubMedSearch : Huang_1992_FEMS.Microbiol.Lett_76_267
PubMedID: 1427017
Gene_locus related to this paper: pseae-Y2218