Pan Y

References (45)

Title : Screening of Active Substances Regulating Alzheimer's Disease in Ginger and Visualization of the Effectiveness on 6-Gingerol Pathway Targets - Pan_2024_Foods_13_
Author(s) : Pan Y , Li Z , Zhao X , Du Y , Zhang L , Lu Y , Yang L , Cao Y , Qiu J , Qian Y
Ref : Foods , 13 : , 2024
Abstract : Ginger has been reported to potentially treat Alzheimer's disease (AD), but the specific compounds responsible for this biological function and their mechanisms are still unknown. In this study, a combination of network pharmacology, molecular docking, and dynamic simulation technology was used to screen active substances that regulate AD and explore their mechanisms. The TCMSP, GeneCards, OMIM, and DisGeNET databases were utilized to obtain 95 cross-targets related to ginger's active ingredients and AD as key targets. A functional enrichment analysis revealed that the pathways in which ginger's active substances may be involved in regulating AD include response to exogenous stimuli, response to oxidative stress, response to toxic substances, and lipid metabolism, among others. Furthermore, a drug-active ingredient-key target interaction network diagram was constructed, highlighting that 6-Gingerol is associated with 16 key targets. Additionally, a protein-protein interaction (PPI) network was mapped for the key targets, and HUB genes (ALB, ACTB, GAPDH, CASP3, and CAT) were identified. Based on the results of network pharmacology and cell experiments, 6-Gingerol was selected as the active ingredient for further investigation. Molecular docking was performed between 6-Gingerol and its 16 key targets, and the top three proteins with the strongest binding affinities (ACHE, MMP2, and PTGS2) were chosen for molecular dynamics analysis together with the CASP3 protein as the HUB gene. The findings indicate that 6-Gingerol exhibits strong binding ability to these disease targets, suggesting its potential role in regulating AD at the molecular level, as well as in abnormal cholinesterase metabolism and cell apoptosis, among other related regulatory pathways. These results provide a solid theoretical foundation for future in vitro experiments using actual cells and animal experiments to further investigate the application of 6-Gingerol.
ESTHER : Pan_2024_Foods_13_
PubMedSearch : Pan_2024_Foods_13_
PubMedID: 38397589

Title : Design, synthesis, and evaluation of dual-target inhibitors for the treatment of Alzheimer's disease - Zhai_2024_Arch.Pharm.(Weinheim)__e2300693
Author(s) : Zhai J , Hao C , Wang X , Cao Y , Pan Y , Zhou M , Sun J , Li C
Ref : Arch Pharm (Weinheim) , :e2300693 , 2024
Abstract : Abeta(1-42) and acetylcholinesterase (AChE) are two key therapeutic targets for Alzheimer's disease (AD). The purpose of this study is to develop a dual-target inhibitor that inhibits both of these targets by fusing the chemical structure of baicalein and donepezil. Among them, we modified the structure of baicalein to arylcoumarin, synthesized three kinds of structural compounds, and evaluated their biological activities. The results showed that compound 3b had the strongest inhibitory effect on AChE (IC(50) = 0.05 +/- 0.02 microM), which was better than those of donepezil and baicalein. In addition, compound 3b has a strong ability to inhibit the aggregation of Abeta(1-42) and protect nerve cells, and it can also penetrate the blood-brain barrier well. Using a zebrafish behavioral analyzer test, it was found that compound 3b can alleviate the behavioral effects of AlCl(3) -induced zebrafish larval movement retardation, which has a certain guiding significance for simulating the movement disorders of AD patients. In summary, compound 3b is expected to become a multifunctional agent for treating and alleviating the symptoms of AD patients.
ESTHER : Zhai_2024_Arch.Pharm.(Weinheim)__e2300693
PubMedSearch : Zhai_2024_Arch.Pharm.(Weinheim)__e2300693
PubMedID: 38332316

Title : The effect of double filtration plasmapheresis and corticosteroids on patients with anti-dipeptidyl-peptidase-like protein 6 encephalitis - Wan_2024_Ther.Apher.Dial_28_141
Author(s) : Wan W , Pan Y , Chen Y , Bai S , Yao X , Lin Y , Wu J , Ni L , Mei Y , Qiu H , Zhou Y , Hao Y , Guan Y
Ref : Ther Apher Dial , 28 :141 , 2024
Abstract : INTRODUCTION: Anti-dipeptidyl-peptidase-like protein 6 (DPPX) encephalitis is a rare condition with varied symptoms including gastrointestinal issues, weight loss, cognitive and mental dysfunction, and hyperexcitability of the central nervous system. METHODS: We studied five patients with anti-DPPX encephalitis who received immunotherapy, specifically DFPP, at our hospital. We analyzed their clinical symptoms, lab results, electrophysiological and imaging findings, and outcomes with immunotherapy. RESULTS: Patients presented with cognitive dysfunction, tremor, seizures, psychiatric disturbances, and cerebellar and brainstem dysfunction. Magnetic resonance imaging (MRI) showed brain abnormalities in one patient and elevated cerebrospinal fluid (CSF) protein levels in two patients. Antibodies against DPPX were detected in all patients and in CSF in two patients. One patient had antibodies against anti-CV2/contactin response mediator protein 5 (CRMP5). All patients responded well to DFPP and corticosteroids. CONCLUSION: DFPP may be an effective treatment for anti-DPPX encephalitis. Further research is needed to understand disease progression and evaluate immunotherapy efficacy.
ESTHER : Wan_2024_Ther.Apher.Dial_28_141
PubMedSearch : Wan_2024_Ther.Apher.Dial_28_141
PubMedID: 37461148
Gene_locus related to this paper: human-DPP6

Title : Therapeutic potential of the medicinal mushroom Ganoderma lucidum against Alzheimer's disease - Chen_2024_Biomed.Pharmacother_172_116222
Author(s) : Chen XJ , Deng Z , Zhang LL , Pan Y , Fu J , Zou L , Bai Z , Xiao X , Sheng F
Ref : Biomed Pharmacother , 172 :116222 , 2024
Abstract : Alzheimer's disease (AD) is a high-incidence neurodegenerative disorder, characterized by cognitive impairment, memory loss, and psychiatric abnormalities. Ganoderma lucidum is a famous medicinal fungus with a long history of dietary intake, containing various bioactive components, and have been documented to exhibit antioxidant, anti-inflammatory, anti-tumor, anti-aging, and immunomodulatory effects, among others. Recent studies have shown that G. lucidum and its components have promising therapeutic potential against AD from various aspects, which can delay the progression of AD, improve cognitive function and quality of life. The underlying mechanisms mainly include inhibiting tau hyperphosphorylation, inhibiting Abeta formation, affecting activated microglia, regulating NF-kappaB/MAPK signalling pathway, inhibiting neuronal apoptosis, modulating immune system, and inhibiting acetylcholinesterase, etc. This paper systematically reviewed the relevant studies on the therapeutic potential of G. lucidum and its active components for treatment of AD, key points related with the mechanism studies and clinical trials have been discussed, and further perspectives have been proposed. Totally, as a natural medicinal mushroom, G. lucidum has the potential to be developed as effective adjuvant for AD treatment owing to its therapeutic efficacy against multiple pathogenesis of AD. Further mechanical investigation and clinical trials can help unlock the complete potential of G. lucidum as a therapeutic option for AD.
ESTHER : Chen_2024_Biomed.Pharmacother_172_116222
PubMedSearch : Chen_2024_Biomed.Pharmacother_172_116222
PubMedID: 38310653

Title : The effect of double filtration plasmapheresis and corticosteroids on patients with anti-dipeptidyl-peptidase-like protein 6 encephalitis - Wan_2023_Ther.Apher.Dial__
Author(s) : Wan W , Pan Y , Chen Y , Bai S , Yao X , Lin Y , Wu J , Ni L , Mei Y , Qiu H , Zhou Y , Hao Y , Guan Y
Ref : Ther Apher Dial , : , 2023
Abstract : INTRODUCTION: Anti-dipeptidyl-peptidase-like protein 6 (DPPX) encephalitis is a rare condition with varied symptoms including gastrointestinal issues, weight loss, cognitive and mental dysfunction, and hyperexcitability of the central nervous system. METHODS: We studied five patients with anti-DPPX encephalitis who received immunotherapy, specifically DFPP, at our hospital. We analyzed their clinical symptoms, lab results, electrophysiological and imaging findings, and outcomes with immunotherapy. RESULTS: Patients presented with cognitive dysfunction, tremor, seizures, psychiatric disturbances, and cerebellar and brainstem dysfunction. Magnetic resonance imaging (MRI) showed brain abnormalities in one patient and elevated cerebrospinal fluid (CSF) protein levels in two patients. Antibodies against DPPX were detected in all patients and in CSF in two patients. One patient had antibodies against anti-CV2/contactin response mediator protein 5 (CRMP5). All patients responded well to DFPP and corticosteroids. CONCLUSION: DFPP may be an effective treatment for anti-DPPX encephalitis. Further research is needed to understand disease progression and evaluate immunotherapy efficacy.
ESTHER : Wan_2023_Ther.Apher.Dial__
PubMedSearch : Wan_2023_Ther.Apher.Dial__
PubMedID: 37461148
Gene_locus related to this paper: human-DPP6

Title : Screening of the Active Substances for the Assessment of Walnut Kernel in the Treatment of Scopolamine-Induced AD Animals - Xu_2023_Mol.Nutr.Food.Res__e2200816
Author(s) : Xu X , Song Y , Jiang M , Liu M , Zhang X , Wang D , Pan Y , Ren S , Liu X
Ref : Mol Nutr Food Res , :e2200816 , 2023
Abstract : SCOPE: Alzheimer's disease (AD) has been a challenge and hotspot in the field of neuroscience research due to the high morbidity. As we all know, walnut kernel (WK) ingestion has been linked to benefits to brain health and has the function of improving memory. This study follows the AD model induced by scopolamine to reveal the active fractions and substances of walnut in the treatment of AD. METHODS AND RESULTS: The histopathological analysis and brain tissue biochemistry assay are revealed the active fractions of WK, and this result determines that walnut kernel organic acids have significant therapeutic effect on AD. The strategy of studying ingredients pointed at lesions is integrated to ascertain the selected brain-targeted effective substances of WK for blood-brain barrier by ultra-performance liquid chromatography-quadrupole/electrostatic field orbitrap mass spectrometry, and a total of eight organic acids are figured out definite absorptivity in rat brains. Finally, the binding interaction between the effective substances and target proteins is analyzed by molecular docking, and the main function related active markers are ascertained as glansreginin A, glansreginic acid, ellagic acid, and ellagic acid 4-O-xyloside. CONCLUSIONS: The comprehensive process is helpful to the clinical application of WK as a promising cholinesterase inhibitors for nutritional intervention.
ESTHER : Xu_2023_Mol.Nutr.Food.Res__e2200816
PubMedSearch : Xu_2023_Mol.Nutr.Food.Res__e2200816
PubMedID: 38018298

Title : Ultrasensitive Fluorescence Platform Based on AgNPs In Situ-Incorporated Zr-MOFs for the Detection of Organophosphorus Pesticides - Wang_2023_ACS.Appl.Mater.Interfaces__
Author(s) : Wang L , Pan Y , Wang Z , Wang Y , Wei X
Ref : ACS Appl Mater Interfaces , : , 2023
Abstract : Organophosphorus pesticides (OPPs) are extensively used in agricultural production, and the contamination caused by their residues has raised significant concerns regarding potential threats to human health. Herein, a novel fluorescence nanoprobe based on an enzyme-mediated silver nanoparticle-modified metal organic framework (AgNPs@PCN-224) was successfully prepared for the rapid detection of OPPs. Initially, AgNPs@PCN-224 were synthesized by reducing silver nitrate (AgNO(3)) using sodium borohydride (NaBH(4)) embedded into luminescent PCN-224. This triggered the inner filter effect, leading to fluorescence quenching. Meanwhile, under the catalysis of acetylcholinesterase (AChE) and choline oxidase (CHO), acetylcholine (ATCh) was decomposed to hydrogen peroxide (H(2)O(2)), which could destroy AgNPs to form Ag(+) released from PCN-224 for fluorescence recovery. Instead, fenitrothion, an OPP, inhibited AChE activity, allowing the quenched fluorescence to be reactivated. Under the current optimum conditions, the fluorescence intensity had a good correlation (Y = -728.5370X + 2178.4248, R(2) = 0.9869) over a dynamic range of fenitrothion concentrations from 0.1 to 500 ng/mL, with an LOD of 0.037 ng/mL. In addition, the anti-interference ability and robustness of the proposed sensor was verified for the monitoring of fenitrothion in tea with recoveries of 87.67-103.72% and the relative standard deviations (RSD) < 5.43%, indicating that the system has excellent prospects for OPP determination in practical applications. Furthermore, this work provides a universal platform for screening other enzyme inhibitors to detect OPPs.
ESTHER : Wang_2023_ACS.Appl.Mater.Interfaces__
PubMedSearch : Wang_2023_ACS.Appl.Mater.Interfaces__
PubMedID: 37676637

Title : Inducible Gut-Specific Carboxylesterase SlCOE030 in Polyphagous Pests of Spodoptera litura Conferring Tolerance between Nicotine and Cyantraniliprole - Li_2023_J.Agric.Food.Chem__
Author(s) : Li J , Lv Y , Liu Y , Bi R , Pan Y , Shang Q
Ref : Journal of Agricultural and Food Chemistry , : , 2023
Abstract : Insecticides tolerance in herbivorous arthropods is associated with preadaptation to host plant allelochemicals. However, how plant secondary metabolites activate detoxifying metabolic genes to develop tolerance remains unclear. Herein, the tolerance of Spodoptera litura larvae to cyantraniliprole was increased after nicotine exposure. An S. litura alpha esterase, SlCOE030, was predominantly expressed in the midgut and induced after exposure to cyantraniliprole, nicotine, and cyantraniliprole plus nicotine. Drosophila melanogaster with ectopically overexpressed SlCOE030 enhanced cyantraniliprole and nicotine tolerance by 4.91- and 2.12-fold, respectively. Compared to UAS-SlCOE030 and Esg-GAL4 lines, the Esg > SlCOE030 line laid more eggs after nicotine exposure. SlCOE030 knockdown decreased the sensitivity of nicotine-treated S. litura larvae to cyantraniliprole. Metabolism assays indicated that recombinant SlCOE030 protein metabolizes cyantraniliprole. Homology modeling and molecular docking analysis demonstrated that SlCOE030 exhibits effective affinities for cyantraniliprole and nicotine. Thus, insect CarEs may result in the development of cross-tolerance between synthetic insecticides and plant secondary metabolites.
ESTHER : Li_2023_J.Agric.Food.Chem__
PubMedSearch : Li_2023_J.Agric.Food.Chem__
PubMedID: 36877657
Gene_locus related to this paper: spolt-SlCOE030

Title : MiR-181a-5p facilitates proliferation, invasion, and glycolysis of breast cancer through NDRG2-mediated activation of PTEN\/AKT pathway - Zhai_2022_Bioengineered_13_83
Author(s) : Zhai Z , Mu T , Zhao L , Li Y , Zhu D , Pan Y
Ref : Bioengineered , 13 :83 , 2022
Abstract : Dysregulation of microRNAs (miRNAs) is associated with the occurrence and development of breast cancer. In this research, we explored the involvement of miR-181a-5p in the progression of breast cancer and investigated potential molecular mechanisms. Firstly, the miR-181a-5p and N-myc downstream-regulated gene (NDRG) 2 expression was detected by real-time quantitative polymerase chain reaction. Cellular processes were assessed using Cell Counting Kit 8, Bromodeoxyuridine, colony formation and transwell assays. HK2, PKM2 and LDHA activities were assessed by ELISA. The combination between miR-181a-5p was assessed by dual-luciferase reporter assay and RNA pull-down assay. The results indicated that miR-181a-5p levels were upregulated and NDRG2 levels were downregulated in breast cancer, leading to poor prognosis. Silencing of miR-181a-5p inhibited cell proliferation, invasion, glycolysis, and xenograft tumor growth, while enhanced miR-181a-5p got the opposite results. Furthermore, NDRG2 acts as a target of miR-181a-5p. Knockout of NDRG2 facilitated biological behaviors and meanwhile enhanced phosphorylation (p)-PTEN and p-AKT levels. Rescue experiments showed that restoring NDRG2 abolished the effects caused by miR-181a-5p in breast cancer cells. In conclusion, miR-181a-5p facilitated tumor progression through NDRG2-induced activation of PTEN/AKT signaling pathway of breast cancer, suggesting that focusing on miR-181a-5p may provide new insight for breast cancer therapy.Abbreviations Brdu: Bromodeoxyuridine; CCK-8: Cell Counting Kit-8; miRNA: microRNAs; mut: mutant; RT-qPCR: real-time quantitative polymerase chain reaction; UTR: untranslated region; WT: wild-type.
ESTHER : Zhai_2022_Bioengineered_13_83
PubMedSearch : Zhai_2022_Bioengineered_13_83
PubMedID: 34951340
Gene_locus related to this paper: human-NDRG2

Title : CGI-58 Protein Acts as a Positive Regulator of Triacylglycerol Accumulation in Phaeodactylum tricornutum - Shu_2022_J.Microbiol.Biotechnol_33_1
Author(s) : Shu Q , Pan Y , Hu H
Ref : J Microbiol Biotechnol , 33 :1 , 2022
Abstract : Comparative gene identification-58 (CGI-58) is an activating protein of triacylglycerol (TAG) lipase. It has a variety of catalytic activities whereby it may play different roles in diverse organisms. In this study, a homolog of CGI-58 in Phaeodactylum tricornutum (PtCGI-58) was identified. PtCGI-58 was localized in mitochondria by GFP fusion protein analysis, which is different from the reported subcellular localization of CGI-58 in animals and plants. Respectively, PtCGI-58 overexpression resulted in increased neutral lipid content and TAG accumulation by 42-46% and 21-32%. Likewise, it also increased the relative content of eicosapentaenoic acid (EPA), and in particular, the EPA content in TAGs almost doubled. Transcript levels of genes involved in de novo fatty acid synthesis and mitochondrial beta-oxidation were significantly upregulated in PtCGI-58 overexpression strains compared with wild-type cells. Our findings suggest that PtCGI-58 may mediate the breakdown of lipids in mitochondria and the recycling of acyl chains derived from mitochondrial beta-oxidation into TAG biosynthesis. Moreover, this study potentially illuminates new functions for CGI-58 in lipid homeostasis and provides a strategy to enrich EPA in algal TAGs.
ESTHER : Shu_2022_J.Microbiol.Biotechnol_33_1
PubMedSearch : Shu_2022_J.Microbiol.Biotechnol_33_1
PubMedID: 36524337

Title : Interleukin-6 and YKL-40 predicted recurrent stroke after ischemic stroke or TIA: analysis of 6 inflammation biomarkers in a prospective cohort study - Li_2022_J.Neuroinflammation_19_131
Author(s) : Li J , Lin J , Pan Y , Wang M , Meng X , Li H , Wang Y , Zhao X , Qin H , Liu L
Ref : J Neuroinflammation , 19 :131 , 2022
Abstract : OBJECTIVE: Contribution of individual and combined inflammatory markers in prognosis after stroke was still undefined. We aimed to investigate the association of systemic and local vascular inflammatory markers and recurrent stroke as well as impact on poor functional outcome. METHODS: In this pre-specified substudy of the Third China National Stroke Registry (CNSR-III), 10,472 consecutive acute ischemic stroke or TIA patients with available centralized-measured levels of Interleukin-6 (IL-6), high sensitive C-reactive protein (hsCRP), IL-1 receptor antagonist (IL-1Ra), lipoprotein-associated phospholipase A(2) mass (Lp-PLA(2)) and activity (Lp-PLA(2)-A), and YKL-40 from 171 sites were enrolled. The primary outcomes consisted of stroke recurrence and poor functional outcome defined as modified Rankin Scale (mRS) score of 2-6 within 1 year. RESULTS: There were 1026 (9.8%) and 2395 (23.4%) patients with recurrent stroke and poor functional outcome within 1 year. The highest quartiles of IL-6 (adjusted HR, 1.36; 95% CI 1.13-1.64; P = 0.001), hsCRP (adjusted HR, 1.41; 95% CI 1.17-1.69; P = 0.0003) and YKL-40 (adjusted HR, 1.28; 95% CI 1.06-1.56; P = 0.01) were associated with increased risk of recurrent stroke; and the highest quartiles of IL-6 (adjusted OR 1.93; 95% CI 1.64-2.27; P < 0.0001), IL-1Ra (adjusted OR 1.60; 95% CI 1.37-1.87; P < 0.0001), hsCRP (adjusted OR 1.60; 95% CI 1.37-1.86; P < 0.0001) and YKL-40 (adjusted OR 1.21; 95% CI 1.03-1.42; P = 0.02) were correlated with increased risk of poor functional outcome. In the multivariate stepwise regression analysis including all markers with backward selection, elevated levels of IL-6 or YKL-40 were associated with recurrent stroke (IL6: OR, 1.34; 95% CI 1.19-1.52; P < 0.0001; YKL-40: OR, 1.01; 95% CI 1.01-1.03; P = 0.004) and poor functional outcome (IL6: OR, 1.68; 95% CI 1.46-1.93; P < 0.0001; YKL-40: OR, 1.02; 95% CI 1.01-1.03; P = 0.0001). Adding IL-6 and YKL-40 significantly increased the area under the receiver operating characteristic curves for the prediction models of Essen Stroke Risk Score (0.03, P < 0.0001) and Totaled Health Risks in Vascular Events Score (0.07, P < 0.0001), and yielded continuous net reclassification improvement (19.0%, P < 0.0001; 33.0, P < 0.0001). CONCLUSIONS: In the patients with ischemic stroke or TIA, IL-6 and YKL-40 were independently associated with recurrent stroke and poor functional outcome, and improved risk classification of clinical risk algorithms.
ESTHER : Li_2022_J.Neuroinflammation_19_131
PubMedSearch : Li_2022_J.Neuroinflammation_19_131
PubMedID: 35761288

Title : NF1 mutation drives neuronal activity-dependent initiation of optic glioma - Pan_2021_Nature__
Author(s) : Pan Y , Hysinger JD , Barron T , Schindler NF , Cobb O , Guo X , Yalcin B , Anastasaki C , Mulinyawe SB , Ponnuswami A , Scheaffer S , Ma Y , Chang KC , Xia X , Toonen JA , Lennon JJ , Gibson EM , Huguenard JR , Liau LM , Goldberg JL , Monje M , Gutmann DH
Ref : Nature , : , 2021
Abstract : Neurons have recently emerged as essential cellular constituents of the tumour microenvironment, and their activity has been shown to increase the growth of a diverse number of solid tumours(1). Although the role of neurons in tumour progression has previously been demonstrated(2), the importance of neuronal activity to tumour initiation is less clear-particularly in the setting of cancer predisposition syndromes. Fifteen per cent of individuals with the neurofibromatosis 1 (NF1) cancer predisposition syndrome (in which tumours arise in close association with nerves) develop low-grade neoplasms of the optic pathway (known as optic pathway gliomas (OPGs)) during early childhood(3,4), raising the possibility that postnatal light-induced activity of the optic nerve drives tumour initiation. Here we use an authenticated mouse model of OPG driven by mutations in the neurofibromatosis 1 tumour suppressor gene (Nf1)(5) to demonstrate that stimulation of optic nerve activity increases optic glioma growth, and that decreasing visual experience via light deprivation prevents tumour formation and maintenance. We show that the initiation of Nf1-driven OPGs (Nf1-OPGs) depends on visual experience during a developmental period in which Nf1-mutant mice are susceptible to tumorigenesis. Germline Nf1 mutation in retinal neurons results in aberrantly increased shedding of neuroligin 3 (NLGN3) within the optic nerve in response to retinal neuronal activity. Moreover, genetic Nlgn3 loss or pharmacological inhibition of NLGN3 shedding blocks the formation and progression of Nf1-OPGs. Collectively, our studies establish an obligate role for neuronal activity in the development of some types of brain tumours, elucidate a therapeutic strategy to reduce OPG incidence or mitigate tumour progression, and underscore the role of Nf1mutation-mediated dysregulation of neuronal signalling pathways in mouse models of the NF1 cancer predisposition syndrome.
ESTHER : Pan_2021_Nature__
PubMedSearch : Pan_2021_Nature__
PubMedID: 34040258

Title : Identification of Candidate Carboxylesterases Associated With Odorant Degradation in Holotrichia parallela Antennae Based on Transcriptome Analysis - Yi_2021_Front.Physiol_12_674023
Author(s) : Yi J , Wang S , Wang Z , Wang X , Li G , Zhang X , Pan Y , Zhao S , Zhang J , Zhou JJ , Wang J , Xi J
Ref : Front Physiol , 12 :674023 , 2021
Abstract : Insects rely on their olfactory systems in antennae to recognize sex pheromones and plant volatiles in surrounding environments. Some carboxylesterases (CXEs) are odorant-degrading enzymes (ODEs), degrading odorant signals to protect the olfactory neurons against continuous excitation. However, there is no report about CXEs in Holotrichia parallela, one of the most major agricultural underground pests in China. In the present study, 20 candidate CXEs were identified based on transcriptome analysis of female and male antennae. Sequence alignments and phylogenetic analysis were performed to investigate the characterization of these candidate CXEs. The expression profiles of CXEs were compared by RT-qPCR analysis between olfactory and non-olfactory tissues of both genders. HparCXE4, 11, 16, 17, 18, 19, and 20 were antenna-biased expressed genes, suggesting their possible roles as ODEs. HparCXE6, 10, 11, 13, and 16 showed significantly higher expression profiles in male antennae, whereas HparCXE18 was expressed more in female antennae. This study highlighted candidate CXE genes linked to odorant degradation in antennae, and provided a useful resource for further work on the H. parallela olfactory mechanism and selection of target genes for integrative control of H. parallela.
ESTHER : Yi_2021_Front.Physiol_12_674023
PubMedSearch : Yi_2021_Front.Physiol_12_674023
PubMedID: 34566671

Title : The degraded polysaccharide from Pyropia haitanensis represses amyloid beta peptide-induced neurotoxicity and memory in vivo - Zhang_2020_Int.J.Biol.Macromol_146_725
Author(s) : Zhang Z , Wang X , Pan Y , Wang G , Mao G
Ref : Int J Biol Macromol , 146 :725 , 2020
Abstract : An antioxidant polysaccharide, porphyran, from red algae Pyropia haitanensis, is introduced as a protective agent against neurotoxicity-induced amyloid beta peptide (Abeta) of Alzheimer's disease (AD) mice. Then the activity of acetylcholinesterase (AChE) and choline acetyltransferase (CHAT) in the cortical and hippocampal tissue were examined by colorimetric method. Results showed that porphyran significantly ameliorated the learning and memory impairment induced by Abeta1-40. Biochemical analysis showed that porphyran increased ChAT activity and decreased AChE activity in the cortical and hippocampal tissue. The mechanism may be related with the increase of cerebral acetylcholine content. Porphyran has a potential of developing anti-aging drug.
ESTHER : Zhang_2020_Int.J.Biol.Macromol_146_725
PubMedSearch : Zhang_2020_Int.J.Biol.Macromol_146_725
PubMedID: 31739053

Title : Royal Jelly Ameliorates Behavioral Deficits, Cholinergic System Deficiency, and Autonomic Nervous Dysfunction in Ovariectomized Cholesterol-Fed Rabbits - Pan_2019_Molecules_24_
Author(s) : Pan Y , Xu J , Jin P , Yang Q , Zhu K , You M , Chen M , Hu F
Ref : Molecules , 24 : , 2019
Abstract : Estrogen deficiency after menopause is associated with autonomic nervous changes, leading to memory impairment and increased susceptibility to Alzheimer's disease (AD). Royal jelly (RJ) from honeybees (Apis mellifera) has estrogenic activity. Here, we investigated whether RJ can improve behavior, cholinergic and autonomic nervous function in ovariectomized (OVX) cholesterol-fed rabbits. OVX rabbits on high-cholesterol diet were administered with RJ for 12 weeks. The results showed that RJ could significantly improve the behavioral deficits of OVX cholesterol-fed rabbits and image structure of the brain. RJ reduced body weight, blood lipid, as well as the levels of amyloid-beta (Abeta), acetylcholinesterase (AchE), and malonaldehyde (MDA) in the brain. Moreover, RJ also increased the activities of choline acetyltransferase (ChAT) and superoxide dismutase (SOD) in the brain, and enhanced heart rate variability (HRV) and Baroreflex sensitivity (BRS) in OVX cholesterol-fed rabbits. Furthermore, RJ was also shown to reduce the content of Evans blue and the expression levels of Abeta, beta-site APP cleaving enzyme 1(BACE1), and receptor for advanced glycation end products (RAGE), and increase the expression level of LDL(low density lipoprotein) receptor-related protein 1 (LRP-1) in the brain. Our findings suggested that RJ has beneficial effects in neurological disorders of postmenopausal women, which were associated with reducing cholesterol and Abeta deposition, enhancing the estrogen levels and the activities of cholinergic and antioxidant systems, and ameliorating the blood(-)brain barrier (BBB) permeability and restoring autonomic nervous system.
ESTHER : Pan_2019_Molecules_24_
PubMedSearch : Pan_2019_Molecules_24_
PubMedID: 30909491

Title : Lipase-Catalyzed Synthesis of Sucrose Monolaurate and Its Antibacterial Property and Mode of Action against Four Pathogenic Bacteria - Shao_2018_Molecules_23_
Author(s) : Shao SY , Shi YG , Wu Y , Bian LQ , Zhu YJ , Huang XY , Pan Y , Zeng LY , Zhang RR
Ref : Molecules , 23 : , 2018
Abstract : The aim of this work was to evaluate the antibacterial activities and mode of action of sucrose monolaurate (SML) with a desirable purity, synthesized by Lipozyme TL IM-mediated transesterification in the novel ionic liquid, against four pathogenic bacteria including L. monocytogenes, B. subtilis, S. aureus, and E. coli. The antibacterial activity was determined by minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and the time(-)kill assay. SML showed varying antibacterial activity against tested bacteria with MICs and MBCs of 2.5 and 20 mM for L. monocytogenes, 2.5 and 20 mM for B. subtilis, 10 and 40 mM for S. aureus, respectively. No dramatic inhibition was observed for E. coli at 80 mM SML. Mechanism of bacterial inactivation caused by SML was revealed through comprehensive factors including cell morphology, cellular lysis, membrane permeability, K(+) leakage, zeta potential, intracellular enzyme, and DNA assay. Results demonstrated that bacterial inactivation against Gram-positive bacteria was primarily induced by the pronounced damage to the cell membrane integrity. SML may interact with cytoplasmic membrane to disturb the regulation system of peptidoglycan hydrolase activities to degrade the peptidoglycan layer and form a hole in the layer. Then, the inside cytoplasmic membrane was blown out due to turgor pressure and the cytoplasmic materials inside leaked out. Leakage of intracellular enzyme to the supernatants implied that the cell membrane permeability was compromised. Consequently, the release of K(+) from the cytosol lead to the alterations of the zeta potential of cells, which would disturb the subcellular localization of some proteins, and thereby causing bacterial inactivation. Moreover, remarkable interaction with DNA was also observed. SML at sub-MIC inhibited biofilm formation by these bacteria.
ESTHER : Shao_2018_Molecules_23_
PubMedSearch : Shao_2018_Molecules_23_
PubMedID: 29738519

Title : Influence of Randomly Inserted Feruloyl Esterase A on beta-Glucosidase Activity in Trichoderma reesei - Hou_2017_Appl.Biochem.Biotechnol_183_254
Author(s) : Hou Y , Pan Y , Yan M , He H , Yang Q , Zhong Y
Ref : Appl Biochem Biotechnol , 183 :254 , 2017
Abstract : As a well-known industrial fungus for cellulase production, the strain RUT-C30 of Trichoderma reesei was selected to produce the feruloyl esterase A (FAEA) by a random integration protocol. The strong promoter of cellobiohydrolase 1 (cbh1) gene was used to drive the expression of FAEA. Using double-joint PCR protocol, Pcbh1-faeA-TtrpC expression cassette was successfully constructed and co-transformed into RUT C30 strain of T. reesei. One transformant with high feruloyl esterase yield (3.44 +/- 0.16 IU/mL) was obtained through plate screening and named TrfaeA1. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis of fermentation supernatant from transformant TrfaeA1 showed a distinct protein band appearing at the position of about 34 kDa, indicating that faeA gene has been successfully expressed in T. reesei. Compared with that in original RUT C30 strain, beta-glucosidase production in transformant TrfaeA1 was significantly increased by about 86.4%, reaching 63.2 IU/mL due to the random insertion of faeA. Moreover, the total secretion protein and filter paper activities of the transformant TrfaeA1 were also improved by up to 5.5 and 4.3%, respectively. The present results indicated that the random insertion strategy could be an effective and feasible method to improve and optimize the cellulase system of filamentous fungi.
ESTHER : Hou_2017_Appl.Biochem.Biotechnol_183_254
PubMedSearch : Hou_2017_Appl.Biochem.Biotechnol_183_254
PubMedID: 28236194

Title : Identification of Differentially Expressed microRNAs between the Fenpropathrin Resistant and Susceptible Strains in Tetranychus cinnabarinus - Zhang_2016_PLoS.One_11_e0152924
Author(s) : Zhang Y , Xu Z , Wu Q , Peng M , Liu Y , Liu X , Shi L , Shen G , Pan Y , He L
Ref : PLoS ONE , 11 :e0152924 , 2016
Abstract : The carmine spider mite (Tetranychus cinnabarinus) is one of the most serious pests on crops and its control mainly depends on chemical acaricides. The excessive and improper acaricides use has resulted in mite resistance to many acaricides, including fenpropathrin. Previous studies have indicated fenpropathrin resistance is a complex development process involving many genes, but information on resistance mechanism of post-transcription regulation is rare. Using Illumina sequencing, several categories of sRNAs were identified from susceptible (TS) and fenpropathrin-resistant strains (TR) of T. cinnabarinus, including 75 known microRNAs (miRNAs) and 64 novel miRNAs, whose target genes containing 78592 miRNA-target pairs were predicted by 6 algorithms. Also, 12 significantly differently expressed miRNAs were identified between the TS and TR libraries and RT-qPCR validation also performed a well consistency with sequencing. The targets of significantly differentially expressed miRNAs included 7 glutathione S-transferase, 7 cytochrome P450 and 16 carboxyl/choline esterase genes, their function in fenpropathrin resistance were further analyzed. The present study provides the firstly large-scale characterization of miRNAs in T. cinnabarinus and the comparison between TS and TR strains gives a clue on how miRNA involves in fenpropathrin resistance.
ESTHER : Zhang_2016_PLoS.One_11_e0152924
PubMedSearch : Zhang_2016_PLoS.One_11_e0152924
PubMedID: 27050424

Title : alpha\/beta-Hydrolase domain-containing 6 (ABHD6) negatively regulates the surface delivery and synaptic function of AMPA receptors - Wei_2016_Proc.Natl.Acad.Sci.U.S.A_113_E2695
Author(s) : Wei M , Zhang J , Jia M , Yang C , Pan Y , Li S , Luo Y , Zheng J , Ji J , Chen J , Hu X , Xiong J , Shi Y , Zhang C
Ref : Proc Natl Acad Sci U S A , 113 :E2695 , 2016
Abstract : In the brain, AMPA-type glutamate receptors are major postsynaptic receptors at excitatory synapses that mediate fast neurotransmission and synaptic plasticity. alpha/beta-Hydrolase domain-containing 6 (ABHD6), a monoacylglycerol lipase, was previously found to be a component of AMPA receptor macromolecular complexes, but its physiological significance in the function of AMPA receptors (AMPARs) has remained unclear. The present study shows that overexpression of ABHD6 in neurons drastically reduced excitatory neurotransmission mediated by AMPA but not by NMDA receptors at excitatory synapses. Inactivation of ABHD6 expression in neurons by either CRISPR/Cas9 or shRNA knockdown methods significantly increased excitatory neurotransmission at excitatory synapses. Interestingly, overexpression of ABHD6 reduced glutamate-induced currents and the surface expression of GluA1 in HEK293T cells expressing GluA1 and stargazin, suggesting a direct functional interaction between these two proteins. The C-terminal tail of GluA1 was required for the binding between of ABHD6 and GluA1. Mutagenesis analysis revealed a GFCLIPQ sequence in the GluA1 C terminus that was essential for the inhibitory effect of ABHD6. The hydrolase activity of ABHD6 was not required for the effects of ABHD6 on AMPAR function in either neurons or transfected HEK293T cells. Thus, these findings reveal a novel and unexpected mechanism governing AMPAR trafficking at synapses through ABHD6.
ESTHER : Wei_2016_Proc.Natl.Acad.Sci.U.S.A_113_E2695
PubMedSearch : Wei_2016_Proc.Natl.Acad.Sci.U.S.A_113_E2695
PubMedID: 27114538
Gene_locus related to this paper: human-ABHD6

Title : Arsenicitalea aurantiaca gen. nov., sp. nov., a new member of the family Hyphomicrobiaceae, isolated from high-arsenic sediment - Mu_2016_Int.J.Syst.Evol.Microbiol_66_5478
Author(s) : Mu Y , Zhou L , Zeng XC , Liu L , Pan Y , Chen X , Wang J , Li S , Li WJ , Wang Y
Ref : Int J Syst Evol Microbiol , 66 :5478 , 2016
Abstract : A novel arsenic-resistant bacterium, designated 42-50T, was isolated from the high-arsenic sediment of Jianghan Plain, Hubei Province, China. Phylogenetic and biochemical analysis indicated that this bacterium represents the first species of a novel genus belonging to the family Hyphomicrobiaceae. The 16S rRNA gene of strain 42-50T shares 96.3-94.2, 96.3, 96.2 and 94.9-93.8 % sequence identities to those of species from the genera Devosia, Youhaiella, Paradevosia and Pelagibacterium, respectively. The major cellular fatty acids are C16 : 0, C18 : 0, C18 : 1omega7c 11-methyl and summed feature 8 (comprising C18 : 1omega7c and C18 : 1omega6c). The predominant polar lipids are diphosphatidylglycerol, phosphatidylglycerol and two unidentified glycolipids. The predominant respiratory quinone is ubiquinone-10 (Q-10). The DNA G+C content of strain 42-50T is 73.7 mol%. The distinct phylogenetic lineage and unique cellular fatty acids suggest that strain 42-50T represents a novel species of a new genus affiliated with the family Hyphomicrobiaceae, for which the name Arsenicitalea aurantiaca gen. nov., sp. nov. is proposed. The type strain is 42-50T (=CCTCC AB 2014325T=KCTC 42825T).
ESTHER : Mu_2016_Int.J.Syst.Evol.Microbiol_66_5478
PubMedSearch : Mu_2016_Int.J.Syst.Evol.Microbiol_66_5478
PubMedID: 27902179
Gene_locus related to this paper: 9rhiz-a0a433xfq5

Title : Characteristics of carboxylesterase genes and their expression-level between acaricide-susceptible and resistant Tetranychus cinnabarinus (Boisduval) - Wei_2016_Pestic.Biochem.Physiol_131_87
Author(s) : Wei P , Shi L , Shen G , Xu Z , Liu J , Pan Y , He L
Ref : Pestic Biochem Physiol , 131 :87 , 2016
Abstract : Carboxylesterases (CarEs) play important roles in metabolism and detoxification of dietary and environmental xenobiotics in insects and mites. On the basis of the Tetranychuscinnabarinus transcriptome dataset, 23 CarE genes (6 genes are full sequence and 17 genes are partial sequence) were identified. Synergist bioassay showed that CarEs were involved in acaricide detoxification and resistance in fenpropathrin- (FeR) and cyflumetofen-resistant (CyR) strains. In order to further reveal the relationship between CarE gene's expression and acaricide-resistance in T. cinnabarinus, we profiled their expression in susceptible (SS) and resistant strains (FeR, and CyR). There were 8 and 4 over-expressed carboxylesterase genes in FeR and CyR, respectively, from which the over-expressions were detected at mRNA level, but not DNA level. Pesticide induction experiment elucidated that 4 of 8 and 2 of 4 up-regulated genes were inducible with significance in FeR and CyR strains, respectively, but they could not be induced in SS strain, which indicated that these genes became more enhanced and effective to withstand the pesticides' stress in resistant T. cinnabarinus. Most expression-changed and all inducible genes possess the Abhydrolase_3 motif, which is a catalytic domain for hydrolyzing. As a whole, these findings in current study provide clues for further elucidating the function and regulation mechanism of these carboxylesterase genes in T. cinnabarinus' resistance formation.
ESTHER : Wei_2016_Pestic.Biochem.Physiol_131_87
PubMedSearch : Wei_2016_Pestic.Biochem.Physiol_131_87
PubMedID: 27265830
Gene_locus related to this paper: tetur-t1jth5 , tetur-t1kth5 , tetur-t1kwe1 , tetur-t1kx09 , tetur-t1kxr8 , tetur-t1l430 , tetur-t1kgp1 , tetur-t1l0m8 , tetur-t1knw0 , tetur-t1kgp7 , tetur-t1l013 , tetur-t1jz51 , tetur-t1kg31 , tetur-t1knv9 , tetur-t1jrz3 , tetur-t1k786 , tetur-t1jth6 , tetur-t1jtg9 , tetur-t1kpg7 , tetur-t1jvb8 , tetur-t1kvj7

Title : Transcriptomic comparison of thiamethoxam-resistance adaptation in resistant and susceptible strains of Aphis gossypii Glover - Pan_2014_Comp.Biochem.Physiol.Part.D.Genomics.Proteomics_13C_10
Author(s) : Pan Y , Peng T , Gao X , Zhang L , Yang C , Xi J , Xin X , Bi R , Shang Q
Ref : Comparative Biochemistry & Physiology Part D Genomics Proteomics , 13C :10 , 2014
Abstract : A thiamethoxam-resistant strain of cotton aphid (ThR) strain displayed a 19.35-fold greater resistance to thiamethoxam compared to a susceptible cotton aphid (SS) strain. Solexa sequencing technology was used to investigate differentially expressed genes (DEGs) in cotton aphids in the context of thiamethoxam resistance. A total of 22,569,311 and 21,317,732 clean reads were obtained from the ThR and SS transcriptomes, respectively, and assembled into 35,222 non-redundant (Nr) consensus sequences. The expression of 620 unigenes changed significantly in the ThR libraries compared to the SS strain; 349 genes were up-regulated, and 271 genes were down-regulated (P<=0.001). Expression levels of ribosomal proteins, ATP synthase, cytochrome c oxidase, ecdysteroid UDP-glucosyltransferase and esterase were up-regulated significantly in the ThR strain compared to the SS strain. The genes of cuticle proteins, salivary proteins, and fibroin heavy chain decreased dramatically. One nicotinic acetylcholine receptor (nAChR) alpha subunit was down-regulated in the ThR strain. The expression levels of 10 differentially expressed unigenes were confirmed using real-time RT-PCR, and the observed trends in gene expression matched the Solexa expression profiles. Specific single-nucleotide polymorphisms (SNPs) in nAChRs that cause amino acid substitution were found from the ThR and SS stains respectively. These data illustrate that genetic changes in nAChR genes and up-regulated ribosomal proteins, ecdysteroid UDP-glucosyltransferase, cytochrome c oxidase, esterase and peroxidase may confer the tolerance of resistant cotton aphids to thiamethoxam.
ESTHER : Pan_2014_Comp.Biochem.Physiol.Part.D.Genomics.Proteomics_13C_10
PubMedSearch : Pan_2014_Comp.Biochem.Physiol.Part.D.Genomics.Proteomics_13C_10
PubMedID: 25528611

Title : Extensive Ace2 duplication and multiple mutations on Ace1 and Ace2 are related with high level of organophosphates resistance in Aphis gossypii - Shang_2014_Environ.Toxicol_29_526
Author(s) : Shang Q , Pan Y , Fang K , Xi J , Wong A , Brennan JA , Cao C
Ref : Environ Toxicol , 29 :526 , 2014
Abstract : Aphis gossypii (Glover) has been found to possess multiple mutations in the acetylcholinesterase (AChE) gene (Ace) that might involve target site insensitivity. In vitro functional expression of AChEs reveals that the resistant Ace1 (Ace1R) and Ace2 (Ace2R) were significantly less inhibited by eserine, omethoate, and malaoxon than the susceptible Ace1 (Ace1S) and Ace2 (Ace2S). Furthermore, in both the mutant and susceptible AChEs, Ace2 was significantly less sensitive to eserine, omethoate, and malaoxon than Ace1. These results suggested that both the mutant Ace1 and Ace2 were responsible for omethoate resistance, while the mutant Ace2 played a major role in insecticide resistance. The DNA copy number and transcription level of Ace2 were 1.52- and 1.88-fold higher in the ORR strain than in the OSS strain. Furthermore, the DNA copy number and transcription level of Ace2 were significantly higher than that of Ace1 in either OSS or ORR strains, demonstrating the involvement of Ace2 gene duplication in resistance. Thus, the authors conclude that omethoate resistance in cotton aphids appears to have evolved through a combination of multiple mutations and extensive Ace2R gene duplication. (c) 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 526-533, 2014.
ESTHER : Shang_2014_Environ.Toxicol_29_526
PubMedSearch : Shang_2014_Environ.Toxicol_29_526
PubMedID: 22489048

Title : Draft Genome Sequence of the Haloacid-Degrading Burkholderia caribensis Strain MBA4 - Pan_2014_Genome.Announc_2_e00047
Author(s) : Pan Y , Kong KF , Tsang JS
Ref : Genome Announc , 2 : , 2014
Abstract : Burkholderia caribensis MBA4 was isolated from soil for its ability to utilize 2-haloacid. An inducible haloacid operon, encoding a dehalogenase and a permease, is mainly responsible for the biotransformation. Here, we report the draft genome sequence of this strain.
ESTHER : Pan_2014_Genome.Announc_2_e00047
PubMedSearch : Pan_2014_Genome.Announc_2_e00047
PubMedID: 24558235
Gene_locus related to this paper: burp8-b2jqn3 , 9burk-w4p0d0 , 9burk-i5ccz8 , 9burk-w4ngl2 , 9burk-w4nxj0 , 9burk-a0a0p0rgc0

Title : Fe(3)O(4) magnetic nanoparticle peroxidase mimetic-based colorimetric assay for the rapid detection of organophosphorus pesticide and nerve agent - Liang_2013_Anal.Chem_85_308
Author(s) : Liang M , Fan K , Pan Y , Jiang H , Wang F , Yang D , Lu D , Feng J , Zhao J , Yang L , Yan X
Ref : Analytical Chemistry , 85 :308 , 2013
Abstract : Rapid and sensitive detection methods are in urgent demand for the screening of extensively used organophosphorus pesticides and highly toxic nerve agents for their neurotoxicity. In this study, we developed a novel Fe(3)O(4) magnetic nanoparticle (MNP) peroxidase mimetic-based colorimetric method for the rapid detection of organophosphorus pesticides and nerve agents. The detection assay is composed of MNPs, acetylcholinesterase (AChE), and choline oxidase (CHO). The enzymes AChE and CHO catalyze the formation of H(2)O(2) in the presence of acetylcholine, which then activates MNPs to catalyze the oxidation of colorimetric substrates to produce a color reaction. After incubation with the organophosphorus neurotoxins, the enzymatic activity of AChE was inhibited and produced less H(2)O(2), resulting in a decreased catalytic oxidation of colorimetric substrates over MNP peroxidase mimetics, accompanied by a drop in color intensity. Three organophosphorus compounds were tested on the assay: acephate and methyl-paraoxon as representative organophosphorus pesticides and the nerve agent Sarin. The novel assay displayed substantial color change after incubation in organophosphorus neurotoxins in a concentration-dependent manner. As low as 1 nM Sarin, 10 nM methyl-paraoxon, and 5 muM acephate are easily detected by the novel assay. In conclusion, by employing the peroxidase-mimicking activity of MNPs, the developed colorimetric assay has the potential of becoming a screening tool for the rapid and sensitive assessment of the neurotoxicity of an overwhelming number of organophosphate compounds.
ESTHER : Liang_2013_Anal.Chem_85_308
PubMedSearch : Liang_2013_Anal.Chem_85_308
PubMedID: 23153113

Title : Dechlorination of chloral hydrate is influenced by the biofilm adhesin protein LapA in Pseudomonas putida LF54 - Zhang_2013_Appl.Environ.Microbiol_79_4166
Author(s) : Zhang W , Huhe , Pan Y , Toyofuku M , Nomura N , Nakajima T , Uchiyama H
Ref : Applied Environmental Microbiology , 79 :4166 , 2013
Abstract : LapA is the largest surface adhesion protein of Pseudomonas putida that initiates biofilm formation. Here, by using transposon insertion mutagenesis and a conditional lapA mutant, we demonstrate for the first time that LapA influences chloral hydrate (CH) dechlorination in P. putida LF54.
ESTHER : Zhang_2013_Appl.Environ.Microbiol_79_4166
PubMedSearch : Zhang_2013_Appl.Environ.Microbiol_79_4166
PubMedID: 23603683
Gene_locus related to this paper: psepu-PIP , psepu-PP1500 , psepu-PP4249 , psepu-q9wwz4 , psepu-u2t3m5

Title : Molecular cloning of a novel bioH gene from an environmental metagenome encoding a carboxylesterase with exceptional tolerance to organic solvents - Shi_2013_BMC.Biotechnol_13_13
Author(s) : Shi Y , Pan Y , Li B , He W , She Q , Chen L
Ref : BMC Biotechnol , 13 :13 , 2013
Abstract : ABSTRACT: BACKGROUND: BioH is one of the key enzymes to produce the precursor pimeloyl-ACP to initiate biotin biosynthesis de novo in bacteria. To date, very few bioH genes have been characterized. In this study, we cloned and identified a novel bioH gene, bioHx, from an environmental metagenome by a functional metagenomic approach. The bioHx gene, encoding an enzyme that is capable of hydrolysis of p-nitrophenyl esters of fatty acids, was expressed in Escherichia coli BL21 using the pET expression system. The biochemical property of the purified BioHx protein was also investigated.
RESULTS: Screening of an unamplified metagenomic library with a tributyrin-containing medium led to the isolation of a clone exhibiting lipolytic activity. This clone carried a 4,570-bp DNA fragment encoding for six genes, designated bioF, bioHx, fabG, bioC, orf5 and sdh, four of which were implicated in the de novo biotin biosynthesis. The bioHx gene encodes a protein of 259 aa with a calculated molecular mass of 28.60 kDa, displaying 24-39% amino acid sequence identity to a few characterized bacterial BioH enzymes. It contains a pentapeptide motif (Gly76-Trp77-Ser78-Met79-Gly80) and a catalytic triad (Ser78-His230-Asp202), both of which are characteristic for lipolytic enzymes. BioHx was expressed as a recombinant protein and characterized. The purified BioHx protein displayed carboxylesterase activity, and it was most active on p-nitrophenyl esters of fatty acids substrate with a short acyl chain (C4). Comparing BioHx with other known BioH proteins revealed interesting diversity in their sensitivity to ionic and nonionic detergents and organic solvents, and BioHx exhibited exceptional resistance to organic solvents, being the most tolerant one amongst all known BioH enzymes. This ascribed BioHx as a novel carboxylesterase with a strong potential in industrial applications.
CONCLUSIONS: This study constituted the first investigation of a novel bioHx gene in a biotin biosynthetic gene cluster cloned from an environmental metagenome. The bioHx gene was successfully cloned, expressed and characterized. The results demonstrated that BioHx is a novel carboxylesterase, displaying distinct biochemical properties with strong application potential in industry. Our results also provided the evidence for the effectiveness of functional metagenomic approach for identifying novel bioH genes from complex ecosystem.
ESTHER : Shi_2013_BMC.Biotechnol_13_13
PubMedSearch : Shi_2013_BMC.Biotechnol_13_13
PubMedID: 23413993

Title : Cholinesterase inhibition and depression of the photic after discharge of flash evoked potentials following acute or repeated exposures to a mixture of carbaryl and propoxur - Mwanza_2012_Neurotoxicol_33_332
Author(s) : Mwanza JC , Lyke DF , Hertzberg RC , Haber L , Kohrman-Vincent M , Li R , Pan Y , Lyles RH , Simmons JE , Macmillan DK , Zehr RD , Swank AE , Herr DW
Ref : Neurotoxicology , 33 :332 , 2012
Abstract : Previously, we reported that acute treatment with propoxur or carbaryl decreased the duration of the photic after discharge (PhAD) of flash evoked potentials (FEPs). In the current studies, we compared the effects of acute or repeated exposure to a mixture of carbaryl and propoxur (1:1.45 ratio; propoxur:carbaryl) on the duration of the PhAD and brain ChE activity in Long Evans rats. Animals were exposed (po) either to a single dose (0, 3, 10, 45 or 75 mg/kg), or 14 daily dosages (0, 3, 10, 30, 45 mg/kg), of the mixture. Acute and repeated treatment with 3mg/kg (or greater) of the mixture produced dose-related inhibition of brain ChE activity. Compared to controls, the PhAD duration decreased after acute administration of 75 mg/kg or repeated treatment with 30 mg/kg of the mixture. The linear relationship between the percent of control brain ChE activity and the PhAD duration was similar for both exposure paradigms. Dose-response models for the acute and repeated exposure data did not differ for brain ChE activity or the duration of the PhAD. Repeated treatment with the mixture resulted in slightly less (13-22%) erythrocyte ChE inhibition than acute exposure. Both acute and repeated treatment resulted in dose-additive results for the PhAD duration and less than dose-additive responses (6-16%) for brain ChE activity for the middle range of dosages. Acute treatment resulted in greater than dose-additive erythrocyte ChE inhibition (15-18%) at the highest dosages. In contrast, repeated treatment resulted in less than dose-additive erythrocyte ChE inhibition (16-22%) at the middle dosages. Brain and plasma levels of propoxur and carbaryl did not differ between the acute and repeated dosing paradigms. In summary, a physiological measure of central nervous system function and brain ChE activity had similar responses after acute or repeated treatment with the carbamate mixture, and brain ChE showed only small deviations from dose-additivity. Erythrocyte ChE activity had larger differences between the acute and repeated treatment paradigms, and showed slightly greater deviations from dose-additivity. Because these treatments utilized larger dosages than anticipated environmental exposures, concern for non-additive effects in humans is minimized. The small magnitude of the deviations from dose-additivity also suggest that in the absence of repeated exposure data, results from an acute study of readily reversible carbamate toxicity can be used to estimate the response to repeated daily exposures.
ESTHER : Mwanza_2012_Neurotoxicol_33_332
PubMedSearch : Mwanza_2012_Neurotoxicol_33_332
PubMedID: 22353443

Title : Two plate-based colorimetric assays for screening alpha-amino acid ester hydrolase with high synthesis\/hydrolysis ratio - Wang_2012_Enzyme.Microb.Technol_51_107
Author(s) : Wang L , Ye LJ , Pan Y , Cao Y
Ref : Enzyme Microb Technol , 51 :107 , 2012
Abstract : alpha-Amino acid ester hydrolases (AEHs) are enzymes of interest to the semi-synthesis of beta-lactam antibiotics with alpha-amino, such as cephalexin and cefaclor. An undesired side reaction, the hydrolysis of alpha-amino acid ester, had hindered applications in antibiotics synthesis. Although the enzymes' S/H ratio can be increased by protein engineering, such approaches require a suitable screening assay. Such a screening assay has not yet been described for AEHs. In this paper, we report a 96-well plate format screening procedure for AEHs based on two spectrophotometric assays. To reduce the hydrolysis reaction while maintaining synthesis activity, and to evaluate the effectiveness of the screening strategy, we introduced random mutations in part of the aeh gene from Xanthomonas rubrillineans by error-prone PCR. By a parallel plate-based screening strategy, three mutants with improved S/H ratio, R87L, T132N and N219I, were obtained.
ESTHER : Wang_2012_Enzyme.Microb.Technol_51_107
PubMedSearch : Wang_2012_Enzyme.Microb.Technol_51_107
PubMedID: 22664195

Title : Changing the specificity of alpha-amino acid ester hydrolase toward para-hydroxyl cephalosporins synthesis by site-directed saturation mutagenesis - Ye_2012_Biotechnol.Lett_34_1719
Author(s) : Ye LJ , Wang L , Pan Y , Cao Y
Ref : Biotechnol Lett , 34 :1719 , 2012
Abstract : alpha-Amino acid ester hydrolases AEHs catalyze the synthesis of beta-lactam antibiotics containing an alpha-amino group with decreased activity toward antibiotics with a p-hydroxyl group The AEH gene from Xanthomonas rubrillineans was cloned and expressed in Escherichia coli Based on the crystal structure of the AEH and cefprozil complex 13 residues not directly involved in substrate recognition were mutated individually The resulting 1,300 mutants were screened for activity using cefprozil as a model product based on spectrophotometric assay in a 96-well format Mutants with improved cefprozil synthetic activity revealed the particular importance of positions 87 131 and 175 for specificity The mutant V131S with the highest initial rates of synthesis toward three p-hydroxyl cephalosporins showed 23 17 and 64 increase in maximum product accumulation of cefadroxil cefprozil and cefatrizine respectively.
ESTHER : Ye_2012_Biotechnol.Lett_34_1719
PubMedSearch : Ye_2012_Biotechnol.Lett_34_1719
PubMedID: 22648687

Title : Active site gating and substrate specificity of butyrylcholinesterase and acetylcholinesterase: insights from molecular dynamics simulations - Fang_2011_J.Phys.Chem.B_115_8797
Author(s) : Fang L , Pan Y , Muzyka JL , Zhan CG
Ref : J Phys Chem B , 115 :8797 , 2011
Abstract : Butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) are highly homologous proteins with distinct substrate preferences. In this study we compared the active sites of monomers and tetramers of human BChE and human AChE after performing molecular dynamics (MD) simulations in water-solvated systems. By comparing the conformational dynamics of gating residues of AChE and BChE, we found that the gating mechanisms of the main door of AChE and BChE are responsible for their different substrate specificities. Our simulation of the tetramers of AChE and BChE indicates that both enzymes could have two dysfunctional active sites due to their restricted accessibility to substrates. The further study on catalytic mechanisms of multiple forms of AChE and BChE would benefit from our comparison of the active sites of the monomers and tetramers of both enzymes.
ESTHER : Fang_2011_J.Phys.Chem.B_115_8797
PubMedSearch : Fang_2011_J.Phys.Chem.B_115_8797
PubMedID: 21682268

Title : Whole-genome sequences of four Mycobacterium bovis BCG vaccine strains - Pan_2011_J.Bacteriol_193_3152
Author(s) : Pan Y , Yang X , Duan J , Lu N , Leung AS , Tran V , Hu Y , Wu N , Liu D , Wang Z , Yu X , Chen C , Zhang Y , Wan K , Liu J , Zhu B
Ref : Journal of Bacteriology , 193 :3152 , 2011
Abstract : Mycobacterium bovis Bacille Calmette-Guerin (BCG) is the only vaccine available against tuberculosis (TB). A number of BCG strains are in use, and they exhibit biochemical and genetic differences. We report the genome sequences of four BCG strains representing different lineages, which will help to design more effective TB vaccines.
ESTHER : Pan_2011_J.Bacteriol_193_3152
PubMedSearch : Pan_2011_J.Bacteriol_193_3152
PubMedID: 21478353
Gene_locus related to this paper: myctu-RV1215C

Title : Nonclassical protein secretion by Bacillus subtilis in the stationary phase is not due to cell lysis - Yang_2011_J.Bacteriol_193_5607
Author(s) : Yang CK , Ewis HE , Zhang X , Lu CD , Hu HJ , Pan Y , Abdelal AT , Tai PC
Ref : Journal of Bacteriology , 193 :5607 , 2011
Abstract : The carboxylesterase Est55 has been cloned and expressed in Bacillus subtilis strains. Est55, which lacks a classical, cleavable N-terminal signal sequence, was found to be secreted during the stationary phase of growth such that there is more Est55 in the medium than inside the cells. Several cytoplasmic proteins were also secreted in large amounts during late stationary phase, indicating that secretion in B. subtilis is not unique to Est55. These proteins, which all have defined cytoplasmic functions, include GroEL, DnaK, enolase, pyruvate dehydrogenase subunits PdhB and PdhD, and SodA. The release of Est55 and those proteins into the growth medium is not due to gross cell lysis, a conclusion that is supported by several lines of evidence: constant cell density and secretion in the presence of chloramphenicol, constant viability count, the absence of EF-Tu and SecA in the culture medium, and the lack of effect of autolysin-deficient mutants. The shedding of these proteins by membrane vesicles into the medium is minimal. More importantly, we have identified a hydrophobic alpha-helical domain within enolase that contributes to its secretion. Thus, upon the genetic deletion or replacement of a potential membrane-embedding domain, the secretion of plasmid gene-encoded mutant enolase is totally blocked, while the wild-type chromosomal enolase is secreted normally in the same cultures during the stationary phase, indicating differential specificity. We conclude that the secretion of Est55 and several cytoplasmic proteins without signal peptides in B. subtilis is a general phenomenon and is not a consequence of cell lysis or membrane shedding; instead, their secretion is through a process(es) in which protein domain structure plays a contributing factor.
ESTHER : Yang_2011_J.Bacteriol_193_5607
PubMedSearch : Yang_2011_J.Bacteriol_193_5607
PubMedID: 21856851

Title : Down-regulated transcriptional level of Ace1 combined with mutations in Ace1 and Ace2 of Aphis gossypii are related with omethoate resistance - Pan_2010_Chem.Biol.Interact_188_553
Author(s) : Pan Y , Shang Q , Fang K , Zhang J , Xi J
Ref : Chemico-Biological Interactions , 188 :553 , 2010
Abstract : The degree of insecticide resistance, acetylcholinesterase (AChE) activity kinetics, AChE gene expression and the cDNA sequence of AChE gene were investigated in resistant and relatively susceptible strains of the cotton aphids, Aphis gossypii (Glover). The resistant strain (ORR) exhibited 53.28-fold resistance to omethoate compared to the relatively susceptible strain (OSS) in cotton aphids. AChE activity, V(max) and K(m) were significantly lower in the ORR strain than in the OSS strain (0.13-, 0.04- and 0.31-fold, respectively). Based on analysis of IC(50) indices, enzyme inhibition experiments showed that AChE from the ORR strain was 7.99-, 4.12-, 4.27-, 8.71- and 4.57-fold insensitive to inhibition by eserine, omethoate, paraoxon, paraoxon-methyl and malaoxon than the OSS strain. Sequence analysis indicated that there were no amino acid substitutions in AChEI (Ace1) and AChEII (Ace2) between the OSS and ORR strain. However, when compared with the 81-171B strain (GenBank No. AF502081), we detected two site mutations (S146N and L532P) in Ace1 with high frequency in both the ORR and OSS strains. One conserved mutation (S431F) in Ace2 was also found in both strains when compared with the 171B strain (GenBank No. AJ748114). Measurements of the levels of gene expression for Ace1 and Ace2 in ORR and OSS, as determined by real-time quantitative PCRs, revealed that the relative transcription levels of Ace1 and Ace2 were 0.26- and 1.07-fold, respectively, in the ORR strain as compared to the OSS strain. These results indicate that the altered AChE sensitivity brought about by a decreased transcriptional level of Ace1 mRNA and combined with the site mutants in both Ace1 and Ace2 might be related to omethoate resistance in cotton aphids.
ESTHER : Pan_2010_Chem.Biol.Interact_188_553
PubMedSearch : Pan_2010_Chem.Biol.Interact_188_553
PubMedID: 20692243

Title : Free energy perturbation simulation on transition states and high-activity mutants of human butyrylcholinesterase for (-)-cocaine hydrolysis - Yang_2010_J.Phys.Chem.B_114_10889
Author(s) : Yang W , Pan Y , Fang L , Gao D , Zheng F , Zhan CG
Ref : J Phys Chem B , 114 :10889 , 2010
Abstract : A unified computational approach based on free energy perturbation (FEP) simulations of transition states has been employed to calculate the mutation-caused shifts of the free energy change from the free enzyme to the rate-determining transition state for (-)-cocaine hydrolysis catalyzed by the currently most promising series of mutants of human butyrylcholinesterase (BChE) that contain the A199S/A328W/Y332G mutations. The FEP simulations were followed by Michaelis-Menten kinetics analysis determining the individual k(cat) and K(M) values missing for the A199S/F227A/A328W/Y332G mutant in this series. The calculated mutation-caused shifts of the free energy change from the free enzyme to the rate-determining transition state are in good agreement with the experimental kinetic data, demonstrating that the unified computational approach based on the FEP simulations of the transition states may be valuable for future computational design of new BChE mutants with a further improved catalytic efficiency against (-)-cocaine.
ESTHER : Yang_2010_J.Phys.Chem.B_114_10889
PubMedSearch : Yang_2010_J.Phys.Chem.B_114_10889
PubMedID: 20677742

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

Title : Model of human butyrylcholinesterase tetramer by homology modeling and dynamics simulation - Pan_2009_J.Phys.Chem.B_113_6543
Author(s) : Pan Y , Muzyka JL , Zhan CG
Ref : J Phys Chem B , 113 :6543 , 2009
Abstract : A mutant of human butyrylcholinesterase (BChE) with high activity against cocaine would be highly promising as a drug for therapeutic treatment of cocaine abuse and overdose. It is desirable to design a recombinant BChE mutant with a long half-life in human circulation. Studies showed that BChE subunits can be assembled by a peptide containing the proline-rich attachment domain (PRAD) to form a stable tetramer. The models of BChE tetramer complexed with PRAD with various sequences have been constructed, in the present study, on the basis of homology modeling and molecular dynamics simulation of explicit water-solvated systems. The 3D models enable us to understand how the BChE subunits are arranged in the tetramer and how the tetramerization domain of BChE is associated with PRAD to form a stable tetramer of human BChE. It has been shown that the six conserved hydrophobic residues located on the C-terminal of BChE are responsible for the key electrostatic and hydrophobic interactions between the tetramerization domain of BChE and PRAD. The simulated tetramer structures suggest that mutation of three residues, i.e., Phe547, Met554, and Phe561, to other hydrophobic residues may be beneficial for increasing the binding between the tetramerization domain of BChE and PRAD. Thus, the detailed structural insights obtained from this study may be valuable for rational design of a recombinant BChE tetramer with a longer residence time in circulation.
ESTHER : Pan_2009_J.Phys.Chem.B_113_6543
PubMedSearch : Pan_2009_J.Phys.Chem.B_113_6543
PubMedID: 19402731

Title : Carboxylesterase activity, cDNA sequence, and gene expression in malathion susceptible and resistant strains of the cotton aphid, Aphis gossypii - Pan_2009_Comp.Biochem.Physiol.B.Biochem.Mol.Biol_152_266
Author(s) : Pan Y , Guo H , Gao X
Ref : Comparative Biochemistry & Physiology B Biochem Mol Biol , 152 :266 , 2009
Abstract : Levels of insecticide resistance, carboxylesterase activity, carboxylesterase expression, and the cDNA sequence of carboxylesterase gene were investigated in malathion resistant and susceptible strains of cotton aphids, Aphis gossypii (Glover). The resistant strain (MRR) exhibited 80.6-fold resistance to malathion compared to the susceptible strain (MSS) in cotton aphids. Five substrates, alpha-naphthyl acetate (alpha-NA), beta-naphthyl acetate (beta-NA), alpha-naphthyl propionate (alpha-NPr), alpha-naphthyl butyrate (alpha-NB), alpha-naphthyl caprylate (alpha-NC) and S-methyl thiobutyrate (S-MTB) were used to determine carboxylesterase activity in MRR and MSS strains of cotton aphids. Carboxylesterase activity was significantly higher in MRR strain than in MSS strain, 3.7-fold for alpha-NA, 3.0-fold for beta-NA, 2.0-fold for alpha-NPr, 2.9-fold for alpha-NB and 1.6-fold for alpha-NC, While for S-MTB, there was nearly no difference between the two strains. Two site mutations (K14Q and N354D) with high frequency were also found by sequence analysis in the MRR strain, compared with the MSS strain. The levels of gene expression for carboxylesterase of both MRR and MSS strains were determined by real-time quantitative PCRs. Compared with the MSS strain, the relative transcription levels and gene copy numbers of the carboxylesterase were 1.99- and 4.42-fold in the MRR strain, respectively. These results indicated that the increased expression of the carboxylesterase resulted from the increased transcription levels of carboxylesterase mRNA and gene copy numbers and combined with the site mutants might play role in cotton aphid resistance to malathion.
ESTHER : Pan_2009_Comp.Biochem.Physiol.B.Biochem.Mol.Biol_152_266
PubMedSearch : Pan_2009_Comp.Biochem.Physiol.B.Biochem.Mol.Biol_152_266
PubMedID: 19110065
Gene_locus related to this paper: aphgo-cxest

Title : Free-energy perturbation simulation on transition states and redesign of butyrylcholinesterase - Yang_2009_Biophys.J_96_1931
Author(s) : Yang W , Pan Y , Zheng F , Cho H , Tai HH , Zhan CG
Ref : Biophysical Journal , 96 :1931 , 2009
Abstract : It is recognized that an ideal anti-cocaine treatment is to accelerate cocaine metabolism by producing biologically inactive metabolites via a route similar to the primary cocaine-metabolizing pathway, i.e., butyrylcholinesterase (BChE)-catalyzed hydrolysis of cocaine. BChE mutants with a higher catalytic activity against (-)-cocaine are highly desired for use as an exogenous enzyme in humans. To develop a rational design for high-activity mutants, we carried out free-energy perturbation (FEP) simulations on various mutations of the transition-state structures in addition to the corresponding free-enzyme structures by using an extended FEP procedure. The FEP simulations on the mutations of both the free-enzyme and transition-state structures allowed us to calculate the mutation-caused shift of the free-energy change from the free enzyme (BChE) to the transition state, and thus to theoretically predict the mutation-caused shift of the catalytic efficiency (k(cat)/K(M)). The computational predictions are supported by the kinetic data obtained from the wet experiments, demonstrating that the FEP-based computational design approach is promising for rational design of high-activity mutants of an enzyme. One of the BChE mutants designed and discovered in this study has an approximately 1800-fold improved catalytic efficiency against (-)-cocaine compared to wild-type BChE. The high-activity mutant may be therapeutically valuable.
ESTHER : Yang_2009_Biophys.J_96_1931
PubMedSearch : Yang_2009_Biophys.J_96_1931
PubMedID: 19254552

Title : UBXD4, a UBX-containing protein, regulates the cell surface number and stability of alpha3-containing nicotinic acetylcholine receptors - Rezvani_2009_J.Neurosci_29_6883
Author(s) : Rezvani K , Teng Y , Pan Y , Dani JA , Lindstrom JM , Garcia Gras EA , McIntosh JM , De Biasi M
Ref : Journal of Neuroscience , 29 :6883 , 2009
Abstract : Adaptor proteins are likely to modulate spatially and temporally the trafficking of a number of membrane proteins, including neuronal nicotinic acetylcholine receptors (nAChRs). A yeast two-hybrid screen identified a novel UBX-containing protein, UBXD4, as one of the cytosolic proteins that interact directly with the alpha3 and alpha4 nAChR subunits. The function of UBX-containing proteins is largely unknown. Immunoprecipitation and confocal microscopy confirmed the interaction of UBXD4 with alpha3-containing nAChRs (alpha3* nAChRs) expressed in HEK293 cells, PC12 cells, and rat cortical neurons. Overexpression of UBXD4 in differentiated PC12 cells (dPC12) increased nAChR cell surface expression, especially that of the alpha3beta2 subtype. These findings were corroborated by electrophysiology, immunofluorescent staining, and biotinylation of surface receptors. Silencing of UBXD4 led to a significant reduction of alpha3* nAChRs in rat cortical neurons and dPC12 cells. Biochemical and immunofluorescence studies of endogenous UBXD4 showed that the protein is located in both the ER and cis-Golgi compartments. Our investigations also showed that the alpha3 subunit is ubiquitinated and that UBXD4 can interfere with its ubiquitination and consequent degradation by the proteasome. Our data suggest that UBXD4 modulates the distribution of alpha3* nAChRs between specialized intracellular compartments and the plasma membrane. This effect is achieved by controlling the stability of the alpha3 subunit and, consequently, the number of receptors at the cell surface.
ESTHER : Rezvani_2009_J.Neurosci_29_6883
PubMedSearch : Rezvani_2009_J.Neurosci_29_6883
PubMedID: 19474315

Title : Evolution of the aging brain transcriptome and synaptic regulation - Loerch_2008_PLoS.One_3_e3329
Author(s) : Loerch PM , Lu T , Dakin KA , Vann JM , Isaacs A , Geula C , Wang J , Pan Y , Gabuzda DH , Li C , Prolla TA , Yankner BA
Ref : PLoS ONE , 3 :e3329 , 2008
Abstract : Alzheimer's disease and other neurodegenerative disorders of aging are characterized by clinical and pathological features that are relatively specific to humans. To obtain greater insight into how brain aging has evolved, we compared age-related gene expression changes in the cortex of humans, rhesus macaques, and mice on a genome-wide scale. A small subset of gene expression changes are conserved in all three species, including robust age-dependent upregulation of the neuroprotective gene apolipoprotein D (APOD) and downregulation of the synaptic cAMP signaling gene calcium/calmodulin-dependent protein kinase IV (CAMK4). However, analysis of gene ontology and cell type localization shows that humans and rhesus macaques have diverged from mice due to a dramatic increase in age-dependent repression of neuronal genes. Many of these age-regulated neuronal genes are associated with synaptic function. Notably, genes associated with GABA-ergic inhibitory function are robustly age-downregulated in humans but not in mice at the level of both mRNA and protein. Gene downregulation was not associated with overall neuronal or synaptic loss. Thus, repression of neuronal gene expression is a prominent and recently evolved feature of brain aging in humans and rhesus macaques that may alter neural networks and contribute to age-related cognitive changes.
ESTHER : Loerch_2008_PLoS.One_3_e3329
PubMedSearch : Loerch_2008_PLoS.One_3_e3329
PubMedID: 18830410

Title : Free energy perturbation (FEP) simulation on the transition states of cocaine hydrolysis catalyzed by human butyrylcholinesterase and its mutants - Pan_2007_J.Am.Chem.Soc_129_13537
Author(s) : Pan Y , Gao D , Yang W , Cho H , Zhan CG
Ref : Journal of the American Chemical Society , 129 :13537 , 2007
Abstract : A novel computational protocol based on free energy perturbation (FEP) simulations on both the free enzyme and transition state structures has been developed and tested to predict the mutation-caused shift of the free energy change from the free enzyme to the rate-determining transition state for human butyrylcholinesterase (BChE)-catalyzed hydrolysis of (-)-cocaine. The calculated shift, denoted by DeltaDeltaG(1 --> 2), of such kind of free energy change determines the catalytic efficiency (kcat/KM) change caused by the simulated mutation transforming enzyme 1 to enzyme 2. By using the FEP-based computational protocol, the DeltaDeltaG(1 --> 2) values for the mutations A328W/Y332A --> A328W/Y332G and A328W/Y332G --> A328W/Y332G/A199S were calculated to be -0.22 and -1.94 kcal/mol, respectively. The calculated DeltaDeltaG(1 --> 2) values predict that the change from the A328W/Y332A mutant to the A328W/Y332G mutant should slightly improve the catalytic efficiency and that the change from the A328W/Y332G mutant to the A328W/Y332G/A199S mutant should significantly improve the catalytic efficiency of the enzyme for the (-)-cocaine hydrolysis. The predicted catalytic efficiency increases are supported by the experimental data showing that kcat/KM = 8.5 x 10(6), 1.4 x 10(7), and 7.2 x 10(7) min(-1) M(-1) for the A328W/Y332A, A328W/Y332G, and A328W/Y332G/A199S mutants, respectively. The qualitative agreement between the computational and experimental data suggests that the FEP simulations may provide a promising protocol for rational design of high-activity mutants of an enzyme. The general computational strategy of the FEP simulation on a transition state can be used to study the effects of a mutation on the activation free energy for any enzymatic reaction.
ESTHER : Pan_2007_J.Am.Chem.Soc_129_13537
PubMedSearch : Pan_2007_J.Am.Chem.Soc_129_13537
PubMedID: 17927177

Title : Computational design of a human butyrylcholinesterase mutant for accelerating cocaine hydrolysis based on the transition-state simulation -
Author(s) : Gao D , Cho H , Yang W , Pan Y , Yang G , Tai HH , Zhan CG
Ref : Angew Chem Int Ed Engl , 45 :653 , 2006
PubMedID: 16355430

Title : Computational redesign of human butyrylcholinesterase for anticocaine medication - Pan_2005_Proc.Natl.Acad.Sci.U.S.A_102_16656
Author(s) : Pan Y , Gao D , Yang W , Cho H , Yang G , Tai HH , Zhan CG
Ref : Proc Natl Acad Sci U S A , 102 :16656 , 2005
Abstract : Molecular dynamics was used to simulate the transition state for the first chemical reaction step (TS1) of cocaine hydrolysis catalyzed by human butyrylcholinesterase (BChE) and its mutants. The simulated results demonstrate that the overall hydrogen bonding between the carbonyl oxygen of (-)-cocaine benzoyl ester and the oxyanion hole of BChE in the TS1 structure for (-)-cocaine hydrolysis catalyzed by A199S/S287G/A328W/Y332G BChE should be significantly stronger than that in the TS1 structure for (-)-cocaine hydrolysis catalyzed by the WT BChE and other simulated BChE mutants. Thus, the transition-state simulations predict that A199S/S287G/A328W/Y332G mutant of BChE should have a significantly lower energy barrier for the reaction process and, therefore, a significantly higher catalytic efficiency for (-)-cocaine hydrolysis. The theoretical prediction has been confirmed by wet experimental tests showing an approximately (456 +/- 41)-fold improved catalytic efficiency of A199S/S287G/A328W/Y332G BChE against (-)-cocaine. This is a unique study to design an enzyme mutant based on transitionstate simulation. The designed BChE mutant has the highest catalytic efficiency against cocaine of all of the reported BChE mutants, demonstrating that the unique design approach based on transition-state simulation is promising for rational enzyme redesign and drug discovery.
ESTHER : Pan_2005_Proc.Natl.Acad.Sci.U.S.A_102_16656
PubMedSearch : Pan_2005_Proc.Natl.Acad.Sci.U.S.A_102_16656
PubMedID: 16275916

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