Feng Y

References (77)

Title : Design, synthesis, and activity evaluation of novel multitargeted l-tryptophan derivatives with powerful antioxidant activity against Alzheimer's disease - Zeng_2024_Arch.Pharm.(Weinheim)__e2300603
Author(s) : Zeng X , Cheng S , Li H , Yu H , Cui Y , Fang Y , Yang S , Feng Y
Ref : Arch Pharm (Weinheim) , :e2300603 , 2024
Abstract : Alzheimer's disease (AD) is a multifactorial neurological disease, and the multitarget directed ligand (MTDL) strategy may be an effective approach to delay its progression. Based on this strategy, 27 derivatives of l-tryptophan, 3a-1-3d-1, were designed, synthesized, and evaluated for their biological activity. Among them, IC(50) (inhibitor concentration resulting in 50% inhibitory activity) values of compounds 3a-18 and 3b-1 were 0.58 and 0.44 microM for human serum butyrylcholinesterase (hBuChE), respectively, and both of them exhibited more than 30-fold selectivity for human serum acetylcholinesterase. Enzyme kinetics studies showed that these two compounds were mixed inhibitors of hBuChE. In addition, these two derivatives possessed extraordinary antioxidant activity in OH radical scavenging and oxygen radical absorption capacity fluorescein assays. Meanwhile, these compounds could also prevent beta-amyloid (Abeta) self-aggregation and possessed low toxicity on PC12 and AML12 cells. Molecular modeling studies revealed that these two compounds could interact with the choline binding site, acetyl binding site, and peripheral anionic site to exert submicromolar BuChE inhibitory activity. In the vitro blood-brain barrier permeation assay, compounds 3a-18 and 3b-1 showed enough blood-brain barrier permeability. In drug-likeness prediction, compounds 3a-18 and 3b-1 showed good gastrointestinal absorption and a low risk of human ether-a-go-go-related gene toxicity. Therefore, compounds 3a-18 and 3b-1 are potential multitarget anti-AD lead compounds, which could work as powerful antioxidants with submicromolar selective inhibitory activity for hBuChE as well as prevent Abeta self-aggregation.
ESTHER : Zeng_2024_Arch.Pharm.(Weinheim)__e2300603
PubMedSearch : Zeng_2024_Arch.Pharm.(Weinheim)__e2300603
PubMedID: 38290060

Title : ANGPTL3 accelerates atherosclerotic progression via direct regulation of M1 macrophage activation in plaque - Zhang_2024_J.Adv.Res__
Author(s) : Zhang Y , Yan C , Dong Y , Zhao J , Yang X , Deng Y , Su L , Yin J , Sun F , Feng Y
Ref : J Adv Res , : , 2024
Abstract : INTRODUCTION: The N-terminal domain of angiopoietin-like protein 3 (ANGPTL3) inhibits lipoprotein lipase activity. Its C-terminal fibrinogen-like (FBN) domain is a ligand of macrophage integrin alphavbeta3. OBJECTIVES: ANGPTL3 might home to plaque where it directly regulates macrophage function via integrin alphavbeta3 for atherosclerosis progression. METHODS: Ldlr(-/-) mice on a high-fat diet and ApoE(-/-) mice on a chow diet were received adeno-associated virus (AAV)-mediated Angptl3 gene transfer and followed up for 12 weeks. ApoE(-/-) mice were injected AAV containing FLAG-tagged Angptl3 cDNA for tracing. Atherosclerotic features were compared between Angptl3(-/-)ApoE(-/-) mice and ApoE(-/-) littermates. THP-1 cells were exposed to 0 or 50 microg/ml ANGPTL3 FBN domain for 24 h to evaluate Toll-like receptor (TLR)4 expression using western blot analysis and circulating cytokine and chemokine profiles by the MILLIPLEX MAP assay. Phospho-proteomic profile was established in ANGPTL3-treated macrophages. Integrin beta3 deficient THP-1 cells were obtained by sgRNAs targeting RGD sequence using Lentivirus-Cas9 system. RESULTS: Angptl3 overexpression increased atherosclerotic progression and CD68(+) macrophages in plaque (p < 0.05 for all). By immunostaining, FLAG(+) cells were identified in plaque of gene transferred ApoE(-/-) mice. Fluorescent immunostaining detected co-localisation of Angptl3 and CD68 in plaque macrophages. Phospho-proteomic analysis revealed that Angptl3 induced phosphorylation of proteins that were involved in the IL-17 signalling pathway in THP-1 cells. In vitro, ANGPTL3 treatment increased the production of interleukin (IL)-1beta and tumour necrosis factor-alpha in THP-1 cells (p < 0.05 for both). Exposure of ANGPTL3 to THP-1 cells induced Akt phosphorylation which was weakened in integrin beta3 deficient ones. ANGPTL3 elevated TLR4 expression via Akt phosphorylation. In response to lipopolysaccharide, nuclear factor-kappaB activity was 2.2-fold higher in THP-1 cells pre-treated with ANGPTL3 than in untreated cells (p < 0.05). CONCLUSIONS: Targeting ANGPTL3 could yield a dual benefit of lowering lipid levels in the blood and suppressing macrophage activation in plaque.
ESTHER : Zhang_2024_J.Adv.Res__
PubMedSearch : Zhang_2024_J.Adv.Res__
PubMedID: 38740260

Title : Aquatic photolysis of high-risk fluorinated liquid crystal monomers: Kinetics, toxicity evaluation, and mechanisms - Wu_2024_Water.Res_255_121510
Author(s) : Wu J , Ye W , Feng Y , Lao W , Li J , Lu H , Liu G , Su G , Deng Y
Ref : Water Res , 255 :121510 , 2024
Abstract : Despite the frequent detection of fluorinated liquid-crystal monomers (FLCMs) in the environment, the level of understanding of their fate, toxicity, and transformation remains insufficient. Herein, we investigated the degradation kinetics and mechanism of an FLCM (4-cyano-3-fluorophenyl 4-ethylbenzoate, CEB-F) under ultraviolet (UV) photolysis in aquatic environment. Our findings demonstrated that the UV photolysis of CEB-F followed first-order kinetics. Photodegradation products were identified using liquid chromatography with mass spectrometry, and detailed reaction pathways were proposed. It is postulated that through the attack of reactive oxygen species, hydroxylation, and CO/C-F bond cleavage, CEB-F gradually degraded into small molecular compounds, releasing fluorine ions. Acute immobilization tests with Daphnia magna (D. magna) revealed significant acute toxicity of CEB-F, with LC(50) values ranging from 1.023 to 0.0536 microM over 24 to 96 h, emphasizing the potential high risk of FLCMs in aquatic ecosystems if inadvertently discharged. Interestingly, we found that the toxicity of CEB-F photolysis reaction solutions was effectively reduced. Through catalase and acetylcholinesterase activities analysis along with molecular docking simulation, we proposed differences in the underlying toxicity mechanisms of CEB-F and its photolysis products to D. magna. These findings highlight the potential harmful effects of FLCMs on aquatic ecosystems and enrich our understanding of the photolysis behavior of FLCMs.
ESTHER : Wu_2024_Water.Res_255_121510
PubMedSearch : Wu_2024_Water.Res_255_121510
PubMedID: 38555780

Title : Recent Progress in the Mechanism and Engineering of alpha\/beta Hydrolases for Chiral Chemical Production - Qiu_2023_Catalysts_13_288
Author(s) : Qiu M , Dong S , Cui Q , Feng Y , Xuan J
Ref : Catalysts , 13 :288 , 2023
Abstract : Chiral compounds are valuable industrial products and intermediates, and the production of chemicals with high enantiopurity is one of the major objects in asymmetric catalysis. Compared with traditional chemical synthesis, enzymatic synthesis can produce chiral molecules under sustainable conditions which are much greener, more economical, and more environmentally friendly. The superfamily of alpha/beta hydrolases includes a lot of diverse enzymes showing excellent chemo-, regio-, and enantio-selectivity in asymmetric synthesis and many of them are biocatalysts in industry. This review outlines the current knowledge of the structures and reaction mechanism of alpha/beta hydrolases and summarizes the screening and protein engineering efforts to develop biocatalysts for chiral chemicals production in recent years. Other strategies such as whole-cell catalysis and protein immobilization to improve the performance of alpha/beta hydrolases are also discussed. The progress in biocatalyst development based on alpha/beta hydrolases will promote the biosynthesis of chiral compounds, thus contributing to the green and sustainable development of the chemical and pharmaceutical industry.
ESTHER : Qiu_2023_Catalysts_13_288
PubMedSearch : Qiu_2023_Catalysts_13_288
PubMedID:

Title : The screening for marine fungal strains with high potential in alkaloids production by in situ colony assay and LC-MS\/MS based secondary metabolic profiling - Lu_2023_Front.Microbiol_14_1144328
Author(s) : Lu T , Liu Y , Zhou L , Liao Q , Nie Y , Wang X , Lei X , Hong P , Feng Y , Hu X , Zhang Y
Ref : Front Microbiol , 14 :1144328 , 2023
Abstract : BACKGROUND: Alkaloids are the second primary class of secondary metabolites (SMs) from marine organisms, most of which have antioxidant, antitumor, antibacterial, anti-inflammatory, and other activities. However, the SMs obtained by traditional isolation strategies have drawbacks such as highly reduplication and weak bioactivity. Therefore, it is significantly important to establish an efficient strategy for screening strains and mining novel compounds. METHODS: In this study, we utilized in situ colony assay combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify the strain with high potential in alkaloids production. The strain was identified by genetic marker genes and morphological analysis. The secondary metabolites from the strain were isolated by the combine use of vacuum liquid chromatography (VLC), ODS column chromatography, and Sephadex LH-20. Their structures were elucidated by 1D/2D NMR, HR-ESI-MS, and other spectroscopic technologies. Finally, these compounds bioactivity were assay, including anti-inflammatory and anti-beta aggregation. RESULTS: Eighteen marine fungi were preliminarily screened for alkaloids production by in situ colony assay using Dragendorff reagent as dye, and nine of them turned orange, which indicated abundant alkaloids. By thin-layer chromatography (TLC), LC-MS/MS, and multiple approaches assisted Feature-Based Molecular Networking (FBMN) analysis of fermentation extracts, a strain ACD-5 (Penicillium mallochii with GenBank accession number OM368350) from sea cucumber gut was selected for its diverse alkaloids profiles especially azaphilones. In bioassays, the crude extracts of ACD-5 in Czapek-dox broth and brown rice medium showed moderate antioxidant, acetylcholinesterase inhibitory, anti-neuroinflammatory, and anti-beta aggregation activities. Three chlorinated azaphilone alkaloids, compounds 1-3 (sclerotioramine, isochromophilone VI, and isochromophilone IX, respectively), were isolated from the fermentation products of ACD-5 in brown rice medium guided by bioactivities and mass spectrometry analysis. Compound 1 had shown remarkable anti-neuroinflammatory activity in liposaccharide induced BV-2 cells. CONCLUSION: In summary, in situ colony screening together with LC-MS/MS, multi-approach assisted FBMN can act as an efficient screening method for strains with potential in alkaloids production.
ESTHER : Lu_2023_Front.Microbiol_14_1144328
PubMedSearch : Lu_2023_Front.Microbiol_14_1144328
PubMedID: 37206330

Title : Engineering a Bacillus subtilis esterase for selective hydrolysis of d, l-menthyl acetate in an organic solvent-free system - Qiao_2023_RSC.Adv_13_10468
Author(s) : Qiao J , Yang D , Feng Y , Wei W , Liu X , Zhang Y , Zheng J , Ying X
Ref : RSC Adv , 13 :10468 , 2023
Abstract : Esterase/lipase-catalyzed selective hydrolysis of d, l-menthyl esters has become one of the promising approaches for producing l-menthol, one of the most important flavoring chemicals with extensive uses. However, the activity and l-enantioselectivity of the biocatalyst are not sufficient for meeting the industrial requirements. Herein, a highly active para-nitrobenzyl esterase from Bacillus subtilis 168 (pnbA-BS) was cloned and then engineered to enhance its l-enantioselectivity. On the basis of the strategy tailoring the steric exclusion effect and structural flexibility of the region adjacent to the substrate, the substitution of Ala400 to Pro caused a remarkable improvement in the E value from 1.0 to 466.6. The variant A400P was purified and further confirmed with strict l-enantioselectivity in the selective hydrolysis of d, l-menthyl acetate, whereas the improved l-enantioselectivity caused decreased activity. To develop an efficient, easy-to-use, and green methodology, organic solvent was omitted and substrate constant feeding was integrated into the whole-cell catalyzed system. During the catalytic process, the selective hydrolysis of 1.0 M d, l-menthyl acetate in 14 h offered a conversion of 48.9%, e.e.(p) value of >99%, and space-time yield of 160.52 g (l d)(-1).
ESTHER : Qiao_2023_RSC.Adv_13_10468
PubMedSearch : Qiao_2023_RSC.Adv_13_10468
PubMedID: 37021103
Gene_locus related to this paper: 9baci-a0a2m8sv47

Title : 4-Methylbenzylidene camphor triggers estrogenic effects via the brain-liver-gonad axis in zebrafish larvae - Xian_2023_Environ.Pollut__122260
Author(s) : Xian H , Li Z , Ye R , Dai M , Feng Y , Bai R , Guo J , Yan X , Yang X , Chen D , Huang Z
Ref : Environ Pollut , :122260 , 2023
Abstract : 4-Methylbenzylidene camphor (4-MBC), an emerging contaminant, is a widely-used ultraviolet (UV) filter incorporated into cosmetics because it protects the skin from UV rays and counters photo-oxidation. Despite the well-established estrogenic activity of 4-MBC, the link between this activity and its effects on neurobehavior and the liver remains unknown. Thus, we exposed zebrafish larvae to environmentally relevant concentrations of 4-MBC with 1.39, 4.17, 12.5 and 15.4 microg/mL from 3 to 5 days postfertilization. We found that 4-MBC produced an estrogenic effect by intensifying fluorescence in the transgenic zebrafish, which was counteracted by co-exposure with estrogen receptor antagonist. 4-MBC-upregulated estrogen receptor alpha (eralpha) mRNA, and an interaction between 4-MBC and ERalpha suggested ERalpha's involvement in the 4-MBC-induced estrogenic activity. RNA sequencing unearthed 4-MBC-triggered responses in estrogen stimulus and lipid metabolism. Additionally, 4-MBC-induced hypoactivity and behavioral phenotypes were dependent on the estrogen receptor (ER) pathway. This may have been associated with the disruption of acetylcholinesterase and acetylcholine activities. As a result, 4-MBC increased vitellogenin expression and caused lipid accumulation in the liver of zebrafish larvae. Collectively, this is the first study to report 4-MBC-caused estrogenic effects through the brain-liver-gonad axis. It provides novel insight into how 4-MBC perturbs the brain and liver development.
ESTHER : Xian_2023_Environ.Pollut__122260
PubMedSearch : Xian_2023_Environ.Pollut__122260
PubMedID: 37506809

Title : Computational design of highly efficient thermostable MHET hydrolases and dual enzyme system for PET recycling - Zhang_2023_Commun.Biol_6_1135
Author(s) : Zhang J , Wang H , Luo Z , Yang Z , Zhang Z , Wang P , Li M , Zhang Y , Feng Y , Lu D , Zhu Y
Ref : Commun Biol , 6 :1135 , 2023
Abstract : Recently developed enzymes for the depolymerization of polyethylene terephthalate (PET) such as FAST-PETase and LCC-ICCG are inhibited by the intermediate PET product mono(2-hydroxyethyl) terephthalate (MHET). Consequently, the conversion of PET enzymatically into its constituent monomers terephthalic acid (TPA) and ethylene glycol (EG) is inefficient. In this study, a protein scaffold (1TQH) corresponding to a thermophilic carboxylesterase (Est30) was selected from the structural database and redesigned in silico. Among designs, a double variant KL-MHETase (I171K/G130L) with a similar protein melting temperature (67.58 degreesC) to that of the PET hydrolase FAST-PETase (67.80 degreesC) exhibited a 67-fold higher activity for MHET hydrolysis than FAST-PETase. A fused dual enzyme system comprising KL-MHETase and FAST-PETase exhibited a 2.6-fold faster PET depolymerization rate than FAST-PETase alone. Synergy increased the yield of TPA by 1.64 fold, and its purity in the released aromatic products reached 99.5%. In large reaction systems with 100 g/L substrate concentrations, the dual enzyme system KL36F achieved over 90% PET depolymerization into monomers, demonstrating its potential applicability in the industrial recycling of PET plastics. Therefore, a dual enzyme system can greatly reduce the reaction and separation cost for sustainable enzymatic PET recycling.
ESTHER : Zhang_2023_Commun.Biol_6_1135
PubMedSearch : Zhang_2023_Commun.Biol_6_1135
PubMedID: 37945666
Gene_locus related to this paper: geost-est30

Title : Crystal structure of the GDSL family esterase EstL5 in complex with PMSF reveals a branch channel of the active site pocket - Chen_2023_Acta.Biochim.Biophys.Sin.(Shanghai)__
Author(s) : Chen R , Gao X , Nie T , Wu J , Wang L , Osman A , Feng Y , Li X , Zhang Y
Ref : Acta Biochim Biophys Sin (Shanghai) , : , 2023
Abstract : Esterases/lipases from the GDSL family have potential applications in the hydrolysis and synthesis of important esters of pharmaceutical, food, and biotechnical interests. However, the structural and functional understanding of GDSL enzymes is still limited. Here, we report the crystal structure of the GDSL family esterase EstL5 complexed with PMSF at 2.34 A resolution. Intriguingly, the PMSF binding site is not located at the active site pocket but is situated in a surface cavity. At the active site, we note that there is a trapped crystallization solvent 1,6-hexanediol, which mimics the bound ester chain, allowing for further definition of the active site pocket of EstL5. The most striking structural feature of EstL5 is the presence of a unique channel, which extends approximately 18.9 A, with a bottleneck radius of 6.8 A, connecting the active-site pocket and the surface cavity. Replacement of Ser205 with the bulk aromatic residue Trp or Phe could partially block the channel at one end and perturb its access. Reduced enzymatic activity is found in the EstL5 S205W and EstL5 S205F mutants, suggesting the functional relevance of the channel to enzyme catalysis. Our study provides valuable information regarding the properties of the GDSL-family enzymes for designing more efficient and robust biocatalysts.
ESTHER : Chen_2023_Acta.Biochim.Biophys.Sin.(Shanghai)__
PubMedSearch : Chen_2023_Acta.Biochim.Biophys.Sin.(Shanghai)__
PubMedID: 37705347

Title : DPP-IV Inhibitory Peptides from Coix Seed Prolamins: Release, Identification, and Analysis of the Interaction between Key Residues and Enzyme Domains - Zhang_2023_J.Agric.Food.Chem__
Author(s) : Zhang S , Li ZM , Feng Y , Yu S , Li Z , Zhang D , Wang C
Ref : Journal of Agricultural and Food Chemistry , : , 2023
Abstract : Dipeptidyl peptidase IV (DPP-IV) inhibitory peptides can regulate type 2 diabetes by inhibiting the cleavage of glucagon-like peptide-1 andv prolonging its half-life. The development of DPP-IV inhibitory peptides is still a hot topic. The primary structure of coix seed prolamins contains peptide sequence fragments that potentially inhibit DPP-IV; however, limited information is available regarding the extraction of peptides from coix seeds and the analysis of their conformational relationships. In this study, novel coix seed prolamin-derived peptides were obtained through single hydrolysis and double-enzyme stepwise hydrolysis. The inhibitory activity of these peptides against DPP-IV was evaluated to explore new functional properties of coix seeds. The results evidenced that the step-by-step enzymolysis (papain and alcalase) compared to single enzymolysis promoted the secondary structure disruption of the hydrolysates, enhanced the beta-turn structure, significantly increased the content of peptides below 1 kDa, and exhibited a substantial increase in DPP-IV inhibitory activity (97% inhibition). Three nontoxic DPP-IV inhibitory peptides, namely, LPFYPN, TFFPQ, and ATFFPQ (IC(50) = 70.24, 176.87, 268.31 microM), were isolated and identified. All three peptides exhibited strong interactions with DPP-IV (all K(A) values >10(3)). LPFYPN exhibited competitive inhibition, while TFFPQ and ATFFPQ demonstrated mixed competitive-noncompetitive inhibition. Hydrogen bonding and hydrophobic interactions were the main contributors to the coix seed prolamin peptides binding to DPP-IV. The central residue was a key amino acid in the parent peptide sequence, forming a more stable Pi-Pi stacking with residues in the active pocket, which may facilitate peptide activity. This study provides theoretical support for the development of coix seed-derived hypoglycemic peptides.
ESTHER : Zhang_2023_J.Agric.Food.Chem__
PubMedSearch : Zhang_2023_J.Agric.Food.Chem__
PubMedID: 37748081

Title : Introducing Mn into ZIF-8 nanozyme for enhancing its catalytic activities and adding specific recognizer for detection of organophosphorus pesticides - Feng_2023_Mikrochim.Acta_190_437
Author(s) : Feng Y , Hu P , Wang M , Sun X , Pan W , Wang J
Ref : Mikrochim Acta , 190 :437 , 2023
Abstract : In order to design and establish a highly efficient and selective nanozyme-based sensing platform for the UV-vis detection of organophosphorus pesticides (OPs), Mn was introduced into ZIF-8 nanozyme for enhancing its catalytic activities and adding specific recognizer. The Mn-doped ZIF-8 (Mn-ZIF-8) nanocomposites were synthesized with a very facile one-pot method by heating the mixture of ZnO, 2-methylimidazole (Hmin) and Mn(CH(3)COO)(2).4H(2)O in a solvent-free system at 180 degreesC for 8 h. The Mn-ZIF-8 nanocomposite showed a higher peroxidase activity and an additional thiocholine (TCh)-degradable property compared to the pristine ZIF-8. OPs could inhibit acetylcholinesterase (AChE) to catalyze the hydrolysis of acetylthiocholine (ATCh) to produce TCh, thus blocking the degradation of Mn-ZIF-8 and protecting the catalysis of the oxidation of colorless 3,3',5,5'-tetramethylbenzydine (TMB) to blue oxidized TMB (ox-TMB). Accordingly, a detection method for OPs with high sensitivity and selectivity was designed and established on the basis of the Mn-ZIF-8 nanozyme with a linear range of 0.1-20 nM and a limit of detection (LOD) as low as 54 pM.
ESTHER : Feng_2023_Mikrochim.Acta_190_437
PubMedSearch : Feng_2023_Mikrochim.Acta_190_437
PubMedID: 37843605

Title : Quinolinones Alkaloids with AChE inhibitory Activity from Mangrove Endophytic Fungus Penicillium citrinum YX-002 - Zhang_2023_Chem.Biodivers__e202300735
Author(s) : Zhang Y , Liu Y , Xue X , Zhou L , Yang W , She Z , Liao Q , Feng Y , Chen X
Ref : Chem Biodivers , :e202300735 , 2023
Abstract : Acetylcholinesterase (AChE) inhibitory activity-guided studies on the mangrove-derived endophytic fungus Penicillium citrinum YX-002 led to the isolation of nine secondary metabolites, including one new quinolinone derivative, quinolactone A (1), a pair of epimers quinolactacin C1 (2) and 3-epi-quinolactacin C1 (3), together with six known analogues (4-9) . Their structures were elucidated based on extensive mass spectrometry (MS) and 1D/2D nuclear magnetic resonance (NMR) spectroscopic analyses, and compared with data in the literature. The absolute configurations of compounds 1-3 was determined by combination of electronic circular dichroism (ECD) calculations and X-Ray single crystal diffraction technique using Cu Kalpha radiation. In bioassays, compounds 1, 4 and 7 showed moderate AChE inhibitory activities with IC50 values of 27.6, 19.4 and 11.2 micromol/L, respectively. The structure-activity relationships (SARs) analysis suggested that the existence of carbonyl group on C-3 and the oxygen atom on the five-membered ring were beneficial to the activity. Molecular docking results showed that compound 7 had a lower affinity interaction energy (-9.3 kcal/mol) with stronger interactions with different sites in AChE activities, which explained its higher activities.
ESTHER : Zhang_2023_Chem.Biodivers__e202300735
PubMedSearch : Zhang_2023_Chem.Biodivers__e202300735
PubMedID: 37423890

Title : Three enigmatic BioH isoenzymes are programmed in the early stage of mycobacterial biotin synthesis, an attractive anti-TB drug target - Xu_2022_PLoS.Pathog_18_e1010615
Author(s) : Xu Y , Yang J , Li W , Song S , Shi Y , Wu L , Sun J , Hou M , Wang J , Jia X , Zhang H , Huang M , Lu T , Gan J , Feng Y
Ref : PLoS Pathog , 18 :e1010615 , 2022
Abstract : Tuberculosis (TB) is one of the leading infectious diseases of global concern, and one quarter of the world's population are TB carriers. Biotin metabolism appears to be an attractive anti-TB drug target. However, the first-stage of mycobacterial biotin synthesis is fragmentarily understood. Here we report that three evolutionarily-distinct BioH isoenzymes (BioH1 to BioH3) are programmed in biotin synthesis of Mycobacterium smegmatis. Expression of an individual bioH isoform is sufficient to allow the growth of an Escherichia coli deltabioH mutant on the non-permissive condition lacking biotin. The enzymatic activity in vitro combined with biotin bioassay in vivo reveals that BioH2 and BioH3 are capable of removing methyl moiety from pimeloyl-ACP methyl ester to give pimeloyl-ACP, a cognate precursor for biotin synthesis. In particular, we determine the crystal structure of dimeric BioH3 at 2.27A, featuring a unique lid domain. Apart from its catalytic triad, we also dissect the substrate recognition of BioH3 by pimeloyl-ACP methyl ester. The removal of triple bioH isoforms (deltabioH1/2/3) renders M. smegmatis biotin auxotrophic. Along with the newly-identified Tam/BioC, the discovery of three unusual BioH isoforms defines an atypical 'BioC-BioH(3)' paradigm for the first-stage of mycobacterial biotin synthesis. This study solves a long-standing puzzle in mycobacterial nutritional immunity, providing an alternative anti-TB drug target.
ESTHER : Xu_2022_PLoS.Pathog_18_e1010615
PubMedSearch : Xu_2022_PLoS.Pathog_18_e1010615
PubMedID: 35816546
Gene_locus related to this paper: mycs2-a0r6y0

Title : Bladder epithelial cell phosphate transporter inhibition protects mice against uropathogenic Escherichia coli infection - Pang_2022_Cell.Rep_39_110698
Author(s) : Pang Y , Cheng Z , Zhang S , Li S , Li X , Zhang X , Feng Y , Cui H , Chen Z , Liu L , Li Q , Huang J , Zhang M , Zhu S , Wang L , Feng L
Ref : Cell Rep , 39 :110698 , 2022
Abstract : Urinary tract infections are predominantly caused by uropathogenic Escherichia coli (UPEC). UPEC infects bladder epithelial cells (BECs) via fusiform vesicles, escapes into the cytosol to evade exocytosis, and establishes intracellular bacterial communities (IBCs) for the next round of infection. The UPEC vesicle escape mechanism remains unclear. Here we show that UPEC senses host immune responses and initiates escape by upregulating a key phospholipase. The UPEC phospholipase PldA disrupts the vesicle membrane, and pldA expression is activated by phosphate reduction in vesicles. The host phosphate transporter PIT1 is located on the fusiform vesicle membrane, transporting phosphate into the cytosol. UPEC infection upregulates PIT1 via nuclear factor kappaB (NF-kappaB), resulting in phosphate reduction. Silencing PIT1 blocks UPEC vesicle escape in BECs, inhibits IBC formation in mouse bladders, and protects mice from UPEC infection. Our results shed light on pathogenic bacteria responding to intracellular phosphate shortage and tackling host defense and provide insights for development of new therapeutic agents to treat UPEC infection.
ESTHER : Pang_2022_Cell.Rep_39_110698
PubMedSearch : Pang_2022_Cell.Rep_39_110698
PubMedID: 35443182

Title : Carbamate-based N-Substituted tryptamine derivatives as novel pleiotropic molecules for Alzheimer's disease - Zhang_2022_Bioorg.Chem_125_105844
Author(s) : Zhang H , Wang Y , Liu D , Li J , Feng Y , Lu Y , Yin G , Li Z , Shi T , Wang Z
Ref : Bioorg Chem , 125 :105844 , 2022
Abstract : A novel series of carbamate-based N-substituted tryptamine derivatives were designed and synthesized based on functional group combination strategy, and possessed both cholinesterase inhibition and neuroprotective effects. After systematically evaluating the cholinesterase inhibitory activity of 24 synthesized compounds, compound 6H6, bearing n-heptyl residue as carbamate moiety, was highlighted due to its great BChE-selective inhibition (eeAChE IC(50) > 100 microM; eqBChE IC(50) = 7 nM), neuronal protection, antioxidation and anti-neuroinflammation efficacy. Cytotoxicity and acute toxicity assays confirmed the safety-efficacy profiles of compound 6H6. Besides, pharmacokinetic properties and blood-brain barrier (BBB) permeability of compound 6H6 were favorable and suitable for further study in vivo. The behavioral tests revealed that compound 6H6 could remarkably improve the scop-induced ethological changes and memory impairment, suggesting compound 6H6, as an attractive pleiotropic molecule, had great promise in treating Alzheimer's disease.
ESTHER : Zhang_2022_Bioorg.Chem_125_105844
PubMedSearch : Zhang_2022_Bioorg.Chem_125_105844
PubMedID: 35594720

Title : The diagnosis of immune-related pancreatitis disguised as multifocal lesions on MRI by endoscopic ultrasound-guided fine-needle biopsy: A case report - Shi_2022_Front.Immunol_13_933595
Author(s) : Shi W , Tan B , Li Y , Zhu L , Feng Y , Jiang Q , Qian J
Ref : Front Immunol , 13 :933595 , 2022
Abstract : Immune checkpoint inhibitor (ICI)-related acute pancreatitis (irAP) is a rare, potentially life-threatening immune-related adverse event. Whereas CT and MRI remain first-line diagnostic imaging modalities, more patients are presenting with atypical irAP as ICI use increases. To appropriately manage these events, it is important to catalog these presentations and provide comprehensive clinical, radiological, and pathological descriptions to guide evidence-based practice. Here, we present the case of a 66-year-old man with advanced lung adenocarcinoma who, after the fifth course of toripalimab, developed epigastric discomfort and elevated serum amylase and lipase. irAP was suspected, but MRI revealed atypical, multifocal pancreatic lesions. To exclude metastases, an endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) was performed. EUS revealed a slightly swollen pancreas with heterogeneous echoic signals and scattered hyperechoic areas in the parenchyma without an obvious mass. Histopathological examination of the FNB revealed retention of the normal lobular pancreatic architecture with focal acinar atrophy associated with a CD8(+) T lymphocyte-predominant infiltrate, further confirming the diagnosis of irAP. After starting glucocorticoids, his symptoms resolved, serum amylase and lipase rapidly decreased to normal, and the abnormal MRI features diminished. irAP can, therefore, present as multifocal lesions on MRI, and, when metastatic disease requires exclusion, EUS-FNB is an effective way to establish a definitive diagnosis. Refining the histopathological and immunopathological criteria for the diagnosis of irAP is now warranted.
ESTHER : Shi_2022_Front.Immunol_13_933595
PubMedSearch : Shi_2022_Front.Immunol_13_933595
PubMedID: 36177047

Title : Improving Effect of the Policosanol from Ericerus pela Wax on Learning and Memory Impairment Caused by Scopolamine in Mice - Sun_2022_Foods_11_
Author(s) : Sun L , Li X , Ma C , He Z , Zhang X , Wang C , Zhao M , Gan J , Feng Y
Ref : Foods , 11 : , 2022
Abstract : Policosanol (PC) is a mixture of long-chain fatty alcohols that exhibits multiple biological activities, such as reducing blood lipid and cholesterol levels, lowering blood pressure, and extenuating liver inflammation. To assess PC's impact on cognitive behavior and function, PC was prepared from Ericerus pela wax using a reduction method and analyzed using gas chromatography (GC). A total of 60 mice were randomly divided into six groups of 10 animals each: control (0.5% CMC-Na solution, i.g.), model (0.5% CMC-Na solution, i.g.), donepezil (3 mg/kg, i.g.), PC low- (2 g/kg, i.g.), medium (4 g/kg, i.g.), and high- (6 g/kg, i.g.) dose groups. All the groups were administered daily for 28 consecutive days. There were four parameters-escape latency, crossings of platform, swimming distance, and time spent in the target quadrant-that were recorded to evaluate the cognitive performance of mice in the Morris Water Maze (MWM). After MWM testing, the levels of acetylcholine (ACh), acetylcholinesterase (AChE), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH) that were present in brain tissue were determined using assay kits. The GC data showed that PC consisted of four major components: tetracosanol (14.40%), hexacosanol (48.97%), octacosanol (25.40%), and triacontanol (4.80%). In the MWM test, PC significantly decreased the escape latency (p < 0.05) and increased the crossings of the platform (p < 0.05) and swimming distance (p < 0.05) and time in the target quadrant (p < 0.05) in rodents compared to that in the model group. Moreover, PC increased the levels of ACh, SOD, and GSH; inhibited AChE; and reduced MDA in the brain tissue of the tested animals. This is the first report to evaluate the efficacy of PC for cognitive behavior and function in animals. Our findings demonstrate that PC from E. pela wax is likely to exert an enhancing effect on learning and memory by promoting the cholinergic system and attenuating oxidative stress, which will provide a new insight into the efficacy of PC and expand its application in the food, nutraceutical, and beverage industries.
ESTHER : Sun_2022_Foods_11_
PubMedSearch : Sun_2022_Foods_11_
PubMedID: 35885338

Title : Sertoli cell survival and barrier function are regulated by miR-181c\/d-Pafah1b1 axis during mammalian spermatogenesis - Feng_2022_Cell.Mol.Life.Sci_79_498
Author(s) : Feng Y , Chen D , Wang T , Zhou J , Xu W , Xiong H , Bai R , Wu S , Li J , Li F
Ref : Cell Mol Life Sciences , 79 :498 , 2022
Abstract : Sertoli cells contribute to the formation of the blood-testis barrier (BTB), which is necessary for normal spermatogenesis. Recently, microRNAs (miRNAs) have emerged as posttranscriptional regulatory elements in BTB function during spermatogenesis. Our previous study has shown that miR-181c or miR-181d (miR-181c/d) is highly expressed in testes from boars at 60 days old compared with at 180 days old. Herein, we found that overexpression of miR-181c/d via miR-181c/d mimics in murine Sertoli cells (SCs) or through injecting miR-181c/d-overexpressing lentivirus in murine testes perturbs BTB function by altering BTB-associated protein distribution at the Sertoli cell-cell interface and F-actin organization, but this in vivo perturbation disappears approximately 6 weeks after the final treatment. We also found that miR-181c/d represses Sertoli cell proliferation and promotes its apoptosis. Moreover, miR-181c/d regulates Sertoli cell survival and barrier function by targeting platelet-activating factor acetylhydrolase 1b regulatory subunit 1 (Pafah1b1) gene. Furthermore, miR-181c/d suppresses PAFAH1B1 expression, reduces the complex of PAFAH1B1 with IQ motif-containing GTPase activating protein 1, and inhibits CDC42/PAK1/LIMK1/Cofilin pathway which is required for F-actin stabilization. In total, our results reveal the regulatory axis of miR-181c/d-Pafah1b1 in cell survival and barrier function of Sertoli cells and provide additional insights into miRNA functions in mammalian spermatogenesis.
ESTHER : Feng_2022_Cell.Mol.Life.Sci_79_498
PubMedSearch : Feng_2022_Cell.Mol.Life.Sci_79_498
PubMedID: 36008729

Title : Development and validation of a LC-MS\/MS method for simultaneous determination of remdesivir and its hydrolyzed metabolite and nucleoside, and its application in a pharmacokinetic study of normal and diabetic nephropathy mice - Yuan_2022_Biomed.Chromatogr__e5380
Author(s) : Yuan M , Hu W , Feng Y , Tong Y , Wang X , Tan B , Xu H , Liu J
Ref : Biomedical Chromatography , :e5380 , 2022
Abstract : Remdesivir (RDV), a phosphoramidate prodrug, has broad-spectrum antiviral activity. It is the first antiviral drug approved by the US Food and Drug Administration (FDA) for the treatment of COVID-19. RDV is rapidly metabolized in the body to produce derivatives: alanine metabolite (RM-442) and RDV C-nucleoside (RN). Here, phosphatase inhibitor PhosSTOP and carboxylesterase inhibitor 5,5'-dithiobis-2-nitrobenzoic acid were used to improve stability of RDV in mouse blood. We developed a rapid and sensitive LC-MS/MS method to simultaneously quantify RDV, RM-442 and RN in mouse blood. Chromatographic separation was achieved by gradient elution on an ACQUITY HSS T(3) column. The run time was 3.2 min. The linearity ranges of the analytes were 0.5-1000 ng/mL for RDV, 5-10000 ng/mL for both RM-442 and RN, respectively. The method had an acceptable precision (RSD < 8.4% for RDV, RSD < 10.7% for RM-442, and RSD < 7.2% for RN) and accuracy (91.0%-106.3% for RDV, 92.5%-98.6% for RM-442, and 87.5%-98.4% for RN). This method was successfully applied to analyze RDV, RM-442 and RN in blood of normal and diabetic nephropathy DBA/2J mice after intravenous injection of RDV 20 mg/kg. The AUC(0-t) of RN between the normal and diabetic nephropathy mice had significant difference (P < 0.01).
ESTHER : Yuan_2022_Biomed.Chromatogr__e5380
PubMedSearch : Yuan_2022_Biomed.Chromatogr__e5380
PubMedID: 35373846

Title : Circular RNA circ_0079593 enhances malignant melanoma progression by the regulation of the miR-573\/ABHD2 axis - Zhao_2021_J.Dermatol.Sci_102_7
Author(s) : Zhao F , Jia Z , Feng Y , Li Z , Feng J
Ref : J Dermatol Sci , 102 :7 , 2021
Abstract : BACKGROUND: Malignant melanoma is the most fatal type of skin tumor. Circular RNAs (circRNAs) have been implicated in the malignant progression of melanoma. OBJECTIVE: The main purpose of this paper was to identify the precise parts of circ_0079593 in the malignant progression of melanoma. METHODS: The levels of circ_0079593, miR-573 and abhydrolase domain containing 2 (ABHD2) were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Cell proliferation, colony formation, cell cycle progression, apoptosis, migration, and invasion were evaluated using the Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, and transwell assays, respectively. Targeted correlations among circ_0079593, miR-573 and ABHD2 were confirmed by dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays. Animal studies were performed to assess the role of circ_0079593 in vivo. RESULTS: Our data showed that circ_0079593 level was up-regulated in melanoma tissues and cells. The knockdown of circ_0079593 suppressed cell proliferation, cell cycle progression, migration, invasion, and enhanced apoptosis in vitro and inhibited tumor growth in vivo. Mechanistically, circ_0079593 directly targeted miR-573, and circ_0079593 controlled ABHD2 expression by miR-573. MiR-573 mediated the regulation of circ_0079593 on melanoma cell progression in vitro. Moreover, ABHD2 was a functional target of miR-573 in regulating melanoma cell progression in vitro. CONCLUSION: Our findings identified that the knockdown of circ_0079593 suppressed melanoma progression at least partially through targeting the miR-573/ABHD2 axis, providing evidence for developing circ_0079593 as a promising therapeutic target for melanoma treatment.
ESTHER : Zhao_2021_J.Dermatol.Sci_102_7
PubMedSearch : Zhao_2021_J.Dermatol.Sci_102_7
PubMedID: 33648800

Title : Synthesis, molecular docking and mosquitocidal efficacy of lawsone and its derivatives against the dengue vector Aedes aegypti L. (Diptera: Culicidae) - Stalin_2021_Med.Chem__
Author(s) : Stalin A , Dhivya P , Lin D , Feng Y , Asharaja AC , Gandhi MR , Kannan BS , Kandhasamy S , Reegan AD , Chen Y
Ref : Med Chem , : , 2021
Abstract : BACKGROUND: Aedes aegypti is the primary dengue vector, a significant public health problem in many countries. Controlling the growth of Ae. aegypti is the biggest challenge in the mosquito control program, and there is a need for finding bioactive molecules to control Ae. aegypti in order to prevent dengue virus transmission. OBJECTIVE: To assess the mosquitocidal property of lawsone and its 3-methyl-4H-chromen-3-yl-1-phenylbenzo[6,7]chromeno[2,3,c]pyrazole-dione derivatives (6a-6h) against various life stages of Ae. aegypti. Besides, to study the mode of action of the active compound by molecular docking and histopathological analysis. METHODS: All derivatives were synthesized from the reaction between 2-hydroxy-1,4-naphthoquinone, chromene-3-carbaldehyde, and 1-phenyl-3-methyl-pyrazol-5-one by using one pot sequential multicomponent reaction. The mosquito life stages were subjected to diverse concentrations ranging from 1.25, 2.5, 5.0, and 10 ppm for lawsone and its derivatives. The structure of all synthesized compounds was characterized by spectroscopic analysis. Docking analysis was performed using autodock tools. Midgut sections of Ae. aegypti larvae were analyzed for histopathological effects. RESULTS: Among the nine compounds screened, derivative 6e showed the highest mortality on Ae. aegypti life stages. The analyzed LC50 and LC90 results of derivative 6e were 3.01, 5.87 ppm, and 3.41, 6.28 ppm on larvae and pupae of Ae. aegypti, respectively. In the ovicidal assay, the derivative 6e recorded 47.2% egg mortality after 96-hour post-exposure to 10 ppm concentration. In molecular docking analysis, the derivative 6e confirmed strong binding interaction (-9.09 kcal/mol and -10.17 kcal/mol) with VAL 60 and HIS 62 of acetylcholinesterase 1 (AChE1) model and LYS 255, LYS 263 of kynurenine aminotransferase of Ae. aegypti, respectively. The histopathological results showed that the derivative 6e affected the columnar epithelial cells (CC) and peritrophic membrane (pM). CONCLUSION: The derivative 6e is highly effective in the life stages of Ae. aegypti mosquito and it could be used in the integrated mosquito management programme.
ESTHER : Stalin_2021_Med.Chem__
PubMedSearch : Stalin_2021_Med.Chem__
PubMedID: 34315380

Title : Algorithm-based coevolution network identification reveals key functional residues of the alpha\/beta hydrolase subfamilies - Wu_2020_FASEB.J_34_1983
Author(s) : Wu Z , Liu H , Xu L , Chen HF , Feng Y
Ref : FASEB Journal , 34 :1983 , 2020
Abstract : Covariant residues identified by computational algorithms have provided new insights into enzyme evolutionary routes. However, the reliability and accuracy of routine statistical coupling analysis (SCA) are unable to satisfy the needs of protein engineering because SCA depends only on sequence information. Here, we set up a new SCA algorithm, SCA.SIM, by integrating structure information and MD simulation data. The more reliable covariant residues with high-quality scores are obtained from sequence alignment weighted by residual movement for eight related subfamilies, belonging to alpha/beta hydrolase family, with Candida antarctica lipase B (CALB). The 38 predicted covariant residues are tested for function by high-throughput quantitative evaluation in combination with activity and thermostability assays of a mutant library and deep sequencing. Based on the landscapes of both activity and thermostability, most mutants play key roles in catalysis, and some mutants gain 2.4- to 6-fold increase in half-life at 50 degrees C and 9- to 12-fold improvement in catalytic efficiency. The activity of double mutants for A225F/T103A is higher than those of A225F and T103A which means that SCA.SIM method might be useful for identifying the allosteric coupling. The SCA.SIM algorithm can be used for protein coevolution and enzyme engineering research.
ESTHER : Wu_2020_FASEB.J_34_1983
PubMedSearch : Wu_2020_FASEB.J_34_1983
PubMedID: 31907985

Title : Protective effect of Soluble Epoxide Hydrolase Inhibition in Retinal Vasculopathy associated with Polycystic Kidney Disease - Lin_2020_Theranostics_10_7857
Author(s) : Lin J , Hu J , Schlotterer A , Wang J , Kolibabka M , Awwad K , Dietrich N , Breitschopf K , Wohlfart P , Kannt A , Lorenz K , Feng Y , Popp R , Hoffmann S , Fleming I , Hammes HP
Ref : Theranostics , 10 :7857 , 2020
Abstract : Rationale: Vasoregression secondary to glial activation develops in various retinal diseases, including retinal degeneration and diabetic retinopathy. Photoreceptor degeneration and subsequent retinal vasoregression, characterized by pericyte loss and acellular capillary formation in the absence diabetes, are also seen in transgenic rats expressing the polycystic kidney disease (PKD) gene. Activated Muller glia contributes to retinal vasodegeneration, at least in part via the expression of the soluble epoxide hydrolase (sEH). Given that an increase in sEH expression triggered vascular destabilization in diabetes, and that vasoregression is similar in diabetic mice and PKD rats, the aim of the present study was to determine whether sEH inhibition could prevent retinal vasoregression in the PKD rat. Methods: One-month old male homozygous transgenic PKD rats were randomly allocated to receive vehicle or a sEH inhibitor (sEH-I; Sar5399, 30 mg/kg) for four weeks. Wild-type Sprague-Dawley (SD) littermates received vehicle as controls. Retinal sEH expression and activity were measured by Western blotting and LC-MS, and vasoregression was quantified in retinal digestion preparations. Microglial activation and immune response cytokines were assessed by immunofluorescence and quantitative PCR, respectively. 19,20-dihydroxydocosapentaenoic acid (19,20-DHDP) mediated Notch signaling, microglial activation and migration were assessed in vivo and in vitro. Results: This study demonstrates that sEH expression and activity were increased in PKD retinae, which led to elevated production of 19,20-DHDP and the depression of Notch signaling. The latter changes elicited pericyte loss and the recruitment of CD11b(+)/CD74(+) microglia to the perivascular region. Microglial activation increased the expression of immune-response cytokines, and reduced levels of Notch3 and delta-like ligand 4 (Dll4). Treatment with Sar5399 decreased 19,20-DHDP generation and increased Notch3 expression. Sar5399 also prevented vasoregression by reducing pericyte loss and suppressed microglial activation as well as the expression of immune-response cytokines. Mechanistically, the activation of Notch signaling by Dll4 maintained a quiescent microglial cell phenotype, i.e. reduced both the surface presentation of CD74 and microglial migration. In contrast, in retinal explants, 19,20-DHDP and Notch inhibition both promoted CD74 expression and reversed the Dll4-induced decrease in migration. Conclusions: Our data indicate that 19,20-DHDP-induced alterations in Notch-signaling result in microglia activation and pericyte loss and contribute to retinal vasoregression in polycystic kidney disease. Moreover, sEH inhibition can ameliorate vasoregression through reduced activity of inflammatory microglia. sEH inhibition is thus an attractive new therapeutic approach to prevent retinal vasoregression.
ESTHER : Lin_2020_Theranostics_10_7857
PubMedSearch : Lin_2020_Theranostics_10_7857
PubMedID: 32685025

Title : Edaravone at high concentrations attenuates cognitive dysfunctions induced by abdominal surgery under general anesthesia in aged mice - Zhou_2020_Metab.Brain.Dis__
Author(s) : Zhou Y , Wu X , Ye L , Bai Y , Zhang H , Xuan Z , Feng Y , Zhang P , Chen Y , Yan Y , Zhu B , Cui W
Ref : Metabolic Brain Disease , : , 2020
Abstract : Postoperative cognitive dysfunction (POCD) is a common neurological disease affecting the elderly patients after surgery. Unfortunately, no effective treatment for this disease has been discovered. Edaravone, a clinical-used free radical scavenger, at 3 mg/kg has been reported to prevent neuroinflammation induced by the combination of surgery and lipopolysaccharide in adult rodents. However, we found that edaravone at such low concentration could not inhibit POCD in aged mice. Instead, edaravone at 33.2 mg/kg significantly prevented recognition and spatial cognitive dysfunctions in 14 month aged mice after abdominal surgery under general anesthesia with isoflurane. Furthermore, edaravone significantly prevented the increase of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) induced by abdominal surgery in aged mice. Edaravone could also decrease glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule-1 (Iba-1) positive areas in the hippocampal regions of surgery mice, suggesting that edaravone might inhibit surgery-induced over-activation of microglia and astrocytes. Moreover, edaravone substantially increased the expression of PSD-95 and pSer9-glycogen synthase kinase-3beta (pSer9-GSK3beta) as demonstrated by Western blotting assay. Furthermore, the activity of acetylcholinesterase (AChE) is decreased in the mice in edaravone group. All these results suggested that edaravone at high concentrations could inhibit surgery-induced cognitive impairments in aged animals, possibly via the attenuation of neuroinflammation, the increase of synaptic proteins, and the elevation of cholinergic transmission, providing a further support that edaravone might be developed as a treatment of POCD.
ESTHER : Zhou_2020_Metab.Brain.Dis__
PubMedSearch : Zhou_2020_Metab.Brain.Dis__
PubMedID: 31916204

Title : Molecular Basis of BioJ, a Unique Gatekeeper in Bacterial Biotin Synthesis - Wei_2019_iScience_19_796
Author(s) : Wei W , Guan H , Zhu T , Zhang S , Fan C , Ouyang S , Feng Y
Ref : iScience , 19 :796 , 2019
Abstract : Biotin is an indispensable cofactor in the three domains of life. The unusual virulence factor BioJ of Francisella catalyzes the formation of pimeloyl-ACP, an intermediate in biotin synthesis. Here, we report the 1.58 A crystal structure of BioJ, the enzymatic activity of which is determined with the in vitro reconstituted reaction and biotin bioassay in vivo. Unlike the paradigm BioH, BioJ displays an atypical alpha/beta-hydrolase fold. A structurally conserved catalytic triad (S151, D248, and H278) of BioJ is functionally defined. A proposed model for BioJ catalysis involves two basic residues-rich cavities, of which cavity-1, rather than cavity-2, binds to the ACP moiety of its physiological substrate, pimeloyl-ACP methyl ester. In summary, this finding provides molecular insights into the BioJ gatekeeper of biotin synthesis.
ESTHER : Wei_2019_iScience_19_796
PubMedSearch : Wei_2019_iScience_19_796
PubMedID: 31494495
Gene_locus related to this paper: 9gamm-BioJ

Title : Network pharmacology study on the active components of Pterocypsela elata and the mechanism of their effect against cerebral ischemia - Niu_2019_Drug.Des.Devel.Ther_13_3009
Author(s) : Niu B , Zhang H , Li C , Yan F , Song Y , Hai G , Jiao Y , Feng Y
Ref : Drug Des Devel Ther , 13 :3009 , 2019
Abstract : Objective: The aim of this study was to identify the active anti-ischemic components of Pterocypsela elata (P. elata) using a network pharmacology approach to construct an effective component anti-cerebral ischemic target network and systematically analyze this medicinal material. Methods: Pharmacological studies have shown that P. elata has an obvious effect against cerebral ischemia. To identify the potential targets, 14 components of P. elata were docked to each structural element of the targets in the DRAR-CPI database by reverse docking technology. We then compared the identified potential targets with FDA-approved targets for stroke/cerebral infarction treatment in the DrugBank database and identified the active components of P. elata and their potential targets for stroke/cerebral infarction treatment. The active component-target networks were constructed using Cytoscape 3.5.1 software. The target protein-protein interactions were analyzed using the STRING database. KEGG pathway analysis and gene ontology (GO) enrichment analysis were performed through the Database for Annotation, Visualization and Integrated Discovery (DAVID). Results: There were 14 active components identified from P. elata and 21 potential targets identified for cerebral ischemia treatment, including carbonic anhydrase 2, ribosyldihydronicotinamide dehydrogenase, cholinesterase, and glutathione S-transferase P. The main involved pathways include metabolic pathways, complement and coagulation cascades and steroid hormone biosynthesis. Conclusion: Through a network pharmacology approach, we predicted the active components of P. elata and their potential targets for cerebral ischemia treatment. Our results provide new perspectives and clues for further studies on the anti-cerebral ischemia mechanism of P. elata.
ESTHER : Niu_2019_Drug.Des.Devel.Ther_13_3009
PubMedSearch : Niu_2019_Drug.Des.Devel.Ther_13_3009
PubMedID: 31564827

Title : A novel ABHD12 nonsense variant in Usher syndrome type 3 family with genotype-phenotype spectrum review - Li_2019_Gene_704_113
Author(s) : Li T , Feng Y , Liu Y , He C , Liu J , Chen H , Deng Y , Li M , Li W , Song J , Niu Z , Sang S , Wen J , Men M , Chen X , Li J , Liu X , Ling J
Ref : Gene , 704 :113 , 2019
Abstract : Usher syndrome (USH) is a clinically common autosomal recessive disorder characterized by retinitis pigmentosa (RP) and sensorineural hearing loss with or without vestibular dysfunction. In this study, we identified a Hunan family of Chinese descent with two affected members clinically diagnosed with Usher syndrome type 3 (USH3) displaying hearing, visual acuity, and olfactory decline. Whole-exome sequencing (WES) identified a nonsense variant in ABHD12 gene that was confirmed to be segregated in this family by Sanger sequencing and exhibited a recessive inheritance pattern. In this family, two patients carried homozygous variant in the ABHD12 (NM_015600: c.249C>G). Mutation of ABHD12, an enzyme that hydrolyzes an endocannabinoid lipid transmitter, caused incomplete PHARC syndrome, as demonstrated in previous reports. Therefore, we also conducted a summary based on variants in ABHD12 in PHARC patients, and in PHARC patients showing that there was no obvious correlation between the genotype and phenotype. We believe that this should be considered during the differential diagnosis of USH. Our findings predicted the potential function of this gene in the development of hearing and vision loss, particularly with regard to impaired signal transmission, and identified a novel nonsense variant to expand the variant spectrum in ABHD12.
ESTHER : Li_2019_Gene_704_113
PubMedSearch : Li_2019_Gene_704_113
PubMedID: 30974196
Gene_locus related to this paper: human-ABHD12

Title : Efficient molecular evolution to generate enantioselective enzymes using a dual-channel microfluidic droplet screening platform - Ma_2018_Nat.Commun_9_1030
Author(s) : Ma F , Chung MT , Yao Y , Nidetz R , Lee LM , Liu AP , Feng Y , Kurabayashi K , Yang GY
Ref : Nat Commun , 9 :1030 , 2018
Abstract : Directed evolution has long been a key strategy to generate enzymes with desired properties like high selectivity, but experimental barriers and analytical costs of screening enormous mutant libraries have limited such efforts. Here, we describe an ultrahigh-throughput dual-channel microfluidic droplet screening system that can be used to screen up to ~10(7) enzyme variants per day. As an example case, we use the system to engineer the enantioselectivity of an esterase to preferentially produce desired enantiomers of profens, an important class of anti-inflammatory drugs. Using two types of screening working modes over the course of five rounds of directed evolution, we identify (from among 5 million mutants) a variant with 700-fold improved enantioselectivity for the desired (S)-profens. We thus demonstrate that this screening platform can be used to rapidly generate enzymes with desired enzymatic properties like enantiospecificity, chemospecificity, and regiospecificity.
ESTHER : Ma_2018_Nat.Commun_9_1030
PubMedSearch : Ma_2018_Nat.Commun_9_1030
PubMedID: 29531246

Title : Antifeedant Activity of Ginkgo biloba Secondary Metabolites against Hyphantria cunea Larvae: Mechanisms and Applications - Pan_2016_PLoS.One_11_e0155682
Author(s) : Pan L , Ren L , Chen F , Feng Y , Luo Y
Ref : PLoS ONE , 11 :e0155682 , 2016
Abstract : Ginkgo biloba is a typical relic plant that rarely suffers from pest hazards. This study analyzed the pattern of G. biloba pest hazards in Beijing; tested the antifeedant activity of G. biloba extracts, including ginkgo flavonoids, ginkgolide, and bilobalide, against Hyphantria cunea larvae; determined the activities of glutathione transferase (GSTs), acetylcholinesterase (AChE), carboxylesterase (CarE) and mixed-functional oxidase (MFO), in larvae after feeding on these G. biloba secondary metabolites; and screened for effective botanical antifeedants in the field. In this study, no indicators of insect infestation were found for any of the examined leaves of G. biloba; all tested secondary metabolites showed significant antifeedant activity and affected the activity of the four larval detoxifying enzymes. Ginkgolide had the highest antifeedant activity and the most significant effect on the detoxifying enzymes (P<0.05). Spraying leaves with G. biloba extracts or ginkgolide both significantly repelled H. cunea larvae in the field (P<0.05), although the former is more economical and practical. This study investigated the antifeedant activity of G. biloba secondary metabolites against H. cunea larvae, and the results provide new insights into the mechanism of G. biloba pest resistance. This study also developed new applications of G. biloba secondary metabolites for effective pest control.
ESTHER : Pan_2016_PLoS.One_11_e0155682
PubMedSearch : Pan_2016_PLoS.One_11_e0155682
PubMedID: 27214257

Title : Sequence homolog-based molecular engineering for shifting the enzymatic pH optimum - Ma_2016_Synth.Syst.Biotechnol_1_195
Author(s) : Ma F , Xie Y , Luo M , Wang S , Hu Y , Liu Y , Feng Y , Yang GY
Ref : Synth Syst Biotechnol , 1 :195 , 2016
Abstract : Cell-free synthetic biology system organizes multiple enzymes (parts) from different sources to implement unnatural catalytic functions. Highly adaption between the catalytic parts is crucial for building up efficient artificial biosynthetic systems. Protein engineering is a powerful technology to tailor various enzymatic properties including catalytic efficiency, substrate specificity, temperature adaptation and even achieve new catalytic functions. However, altering enzymatic pH optimum still remains a challenging task. In this study, we proposed a novel sequence homolog-based protein engineering strategy for shifting the enzymatic pH optimum based on statistical analyses of sequence-function relationship data of enzyme family. By two statistical procedures, artificial neural networks (ANNs) and least absolute shrinkage and selection operator (Lasso), five amino acids in GH11 xylanase family were identified to be related to the evolution of enzymatic pH optimum. Site-directed mutagenesis of a thermophilic xylanase from Caldicellulosiruptor bescii revealed that four out of five mutations could alter the enzymatic pH optima toward acidic condition without compromising the catalytic activity and thermostability. Combination of the positive mutants resulted in the best mutant M31 that decreased its pH optimum for 1.5 units and showed increased catalytic activity at pH < 5.0 compared to the wild-type enzyme. Structure analysis revealed that all the mutations are distant from the active center, which may be difficult to be identified by conventional rational design strategy. Interestingly, the four mutation sites are clustered at a certain region of the enzyme, suggesting a potential 'hot zone' for regulating the pH optima of xylanases. This study provides an efficient method of modulating enzymatic pH optima based on statistical sequence analyses, which can facilitate the design and optimization of suitable catalytic parts for the construction of complicated cell-free synthetic biology systems.
ESTHER : Ma_2016_Synth.Syst.Biotechnol_1_195
PubMedSearch : Ma_2016_Synth.Syst.Biotechnol_1_195
PubMedID: 29062943

Title : Outbred genome sequencing and CRISPR\/Cas9 gene editing in butterflies - Li_2015_Nat.Commun_6_8212
Author(s) : Li X , Fan D , Zhang W , Liu G , Zhang L , Zhao L , Fang X , Chen L , Dong Y , Chen Y , Ding Y , Zhao R , Feng M , Zhu Y , Feng Y , Jiang X , Zhu D , Xiang H , Feng X , Li S , Wang J , Zhang G , Kronforst MR , Wang W
Ref : Nat Commun , 6 :8212 , 2015
Abstract : Butterflies are exceptionally diverse but their potential as an experimental system has been limited by the difficulty of deciphering heterozygous genomes and a lack of genetic manipulation technology. Here we use a hybrid assembly approach to construct high-quality reference genomes for Papilio xuthus (contig and scaffold N50: 492 kb, 3.4 Mb) and Papilio machaon (contig and scaffold N50: 81 kb, 1.15 Mb), highly heterozygous species that differ in host plant affiliations, and adult and larval colour patterns. Integrating comparative genomics and analyses of gene expression yields multiple insights into butterfly evolution, including potential roles of specific genes in recent diversification. To functionally test gene function, we develop an efficient (up to 92.5%) CRISPR/Cas9 gene editing method that yields obvious phenotypes with three genes, Abdominal-B, ebony and frizzled. Our results provide valuable genomic and technological resources for butterflies and unlock their potential as a genetic model system.
ESTHER : Li_2015_Nat.Commun_6_8212
PubMedSearch : Li_2015_Nat.Commun_6_8212
PubMedID: 26354079
Gene_locus related to this paper: papxu-a0a194pj15 , papxu-a0a194q254 , papma-a0a194rdx2 , papxu-a0a194q858 , papxu-a0a194pyl3 , papxu-a0a194q337 , papma-a0a194r1p9 , papma-a0a194r6h1 , papxu-a0a194q1w8 , papma-a0a194ql80 , papma-a0a0n1ipl3 , papma-a0a194qm14

Title : Chronic morphine-induced microRNA-124 promotes microglial immunosuppression by modulating P65 and TRAF6 - Qiu_2015_J.Immunol_194_1021
Author(s) : Qiu S , Feng Y , LeSage G , Zhang Y , Stuart C , He L , Li Y , Caudle Y , Peng Y , Yin D
Ref : J Immunol , 194 :1021 , 2015
Abstract : Opioids have been widely applied in clinics as one of the most potent pain relievers for centuries, but their abuse has deleterious physiological effects including immunosuppression. However, the mechanisms are unclear. TLRs and acetylcholine are widely expressed in the immune and nervous systems, and play critical roles in immune responses. In this article, we show that morphine suppresses the innate immunity in microglia and bone marrow-derived macrophages through differential regulation of TLRs and acetylcholinesterase. Either morphine or inhibition of acetylcholine significantly promotes upregulation of microRNA-124 (miR-124) in microglia, bone marrow-derived macrophages, and the mouse brain, where miR-124 mediates morphine inhibition of the innate immunity by directly targeting a subunit of NF-kappaB p65 and TNFR-associated factor 6 (TRAF6). Furthermore, transcription factors AP-1 and CREB inhibited miR-124, whereas p65 bound directly to promoters of miR-124, thereby enhancing miR-124 transcription. Moreover, acute morphine treatment transiently upregulated the expression of p65 and phospho-p65 in both nucleus and cytoplasm priming the expression of miR-124, whereas long exposure of morphine maintained miR-124 expression, which inhibited p65- and TRAF6-dependent TLR signaling. These data suggest that modulation of miRs is capable of preventing opioid-induced damage to microglia.
ESTHER : Qiu_2015_J.Immunol_194_1021
PubMedSearch : Qiu_2015_J.Immunol_194_1021
PubMedID: 25539811

Title : Structural and functional analysis of a low-temperature-active alkaline esterase from South China Sea marine sediment microbial metagenomic library - Hu_2015_J.Ind.Microbiol.Biotechnol_42_1449
Author(s) : Hu Y , Liu Y , Li J , Feng Y , Lu N , Zhu B , Xue S
Ref : J Ind Microbiol Biotechnol , 42 :1449 , 2015
Abstract : A low-temperature-active alkaline esterase, Est12, from a marine sediment metagenomic fosmid library was identified. Est12 prefers short- and middle-chain p-nitrophenol esters as substrate with optimum temperature and pH value of 50 degrees C and 9.0, respectively, and nearly 50 % of maximum activity retained at 5 degrees C. The hydrolysis activity of Est12 was stable at 40 degrees C. Ca(2+) especially activated the activity of Est12 to about 151 % of the control. DEPC and PMSF inhibited the activity of Est12 to 34 and 25 %, respectively. In addition, Est12 was more tolerable to methanol compared to other organic solvents tested. The crystal structure of Est12 at 1.39 A resolution showed that the cap domain which is composed of an alpha-helix and a flexible region resulted in a relatively wide spectrum of substrate, with p-nitrophenol caproate as the preferred one. Furthermore, the flexible cap domain and the high percentage of Gly, Ser, and Met may play important roles in the adaptation of Est12 to low temperature.
ESTHER : Hu_2015_J.Ind.Microbiol.Biotechnol_42_1449
PubMedSearch : Hu_2015_J.Ind.Microbiol.Biotechnol_42_1449
PubMedID: 26350078
Gene_locus related to this paper: 9bact-b8y562

Title : Characterization of an Enterobacter cloacae Strain Producing both KPC and NDM Carbapenemases by Whole-Genome Sequencing - Wu_2015_Antimicrob.Agents.Chemother_59_6625
Author(s) : Wu W , Feng Y , Carattoli A , Zong Z
Ref : Antimicrobial Agents & Chemotherapy , 59 :6625 , 2015
Abstract : A carbapenem-resistant Enterobacter cloacae strain, WCHECl-14653, causing a fatal bloodstream infection, was characterized by genome sequencing and conjugation experiments. The strain carried two carbapenemase genes, blaNDM-1 and blaKPC-2, on separate IncF plasmids. The coexistence of blaNDM-1 and blaKPC-2 conferred slightly higher-level carbapenem resistance compared with that of blaNDM-1 or blaKPC-2 alone, and the coexistence of two IncF plasmids may generate new platforms for spreading carbapenemase genes.
ESTHER : Wu_2015_Antimicrob.Agents.Chemother_59_6625
PubMedSearch : Wu_2015_Antimicrob.Agents.Chemother_59_6625
PubMedID: 26248381
Gene_locus related to this paper: entcl-a0a0k0npw0

Title : Design of hyperthermophilic lipase chimeras by key motif-directed recombination - Zhou_2015_Chembiochem_16_455
Author(s) : Zhou X , Gao L , Yang G , Liu D , Bai A , Li B , Deng Z , Feng Y
Ref : Chembiochem , 16 :455 , 2015
Abstract : Recombination of diverse natural evolved domains within a superfamily offers greater opportunity for enzyme function leaps. How to recombine protein modules from distant parents with less disruption in cross-interfaces is a challenging issue. Here, we identified the existence of a key motif, the sequence VVSVN(D)YR, within a structural motif psi loop in the alpha/beta-hydrolase fold superfamily, by using a MEME server and the PROMOTIF program. To obtain thermostable lipase-like enzymes, two chimeras were engineered at the key motif regions through recombination of domains from a mesophilic lipase and a hyperthermophilic esterase/peptidase with amino acid identity less than 21 %. The chimeras retained the desirable substrate preference of their mesophilic parent and exhibited more than 100-fold increased thermostability at 50 degrees C. Through site-directed mutation, we further improved activity of the chimera by 4.6-fold. The recombination strategy presented here enables the creation of novel catalysts.
ESTHER : Zhou_2015_Chembiochem_16_455
PubMedSearch : Zhou_2015_Chembiochem_16_455
PubMedID: 25530200

Title : Whole-genome sequencing of cultivated and wild peppers provides insights into Capsicum domestication and specialization - Qin_2014_Proc.Natl.Acad.Sci.U.S.A_111_5135
Author(s) : Qin C , Yu C , Shen Y , Fang X , Chen L , Min J , Cheng J , Zhao S , Xu M , Luo Y , Yang Y , Wu Z , Mao L , Wu H , Ling-Hu C , Zhou H , Lin H , Gonzalez-Morales S , Trejo-Saavedra DL , Tian H , Tang X , Zhao M , Huang Z , Zhou A , Yao X , Cui J , Li W , Chen Z , Feng Y , Niu Y , Bi S , Yang X , Cai H , Luo X , Montes-Hernandez S , Leyva-Gonzalez MA , Xiong Z , He X , Bai L , Tan S , Liu D , Liu J , Zhang S , Chen M , Zhang L , Zhang Y , Liao W , Wang M , Lv X , Wen B , Liu H , Luan H , Yang S , Wang X , Xu J , Li X , Li S , Wang J , Palloix A , Bosland PW , Li Y , Krogh A , Rivera-Bustamante RF , Herrera-Estrella L , Yin Y , Yu J , Hu K , Zhang Z
Ref : Proc Natl Acad Sci U S A , 111 :5135 , 2014
Abstract : As an economic crop, pepper satisfies people's spicy taste and has medicinal uses worldwide. To gain a better understanding of Capsicum evolution, domestication, and specialization, we present here the genome sequence of the cultivated pepper Zunla-1 (C. annuum L.) and its wild progenitor Chiltepin (C. annuum var. glabriusculum). We estimate that the pepper genome expanded approximately 0.3 Mya (with respect to the genome of other Solanaceae) by a rapid amplification of retrotransposons elements, resulting in a genome comprised of approximately 81% repetitive sequences. Approximately 79% of 3.48-Gb scaffolds containing 34,476 protein-coding genes were anchored to chromosomes by a high-density genetic map. Comparison of cultivated and wild pepper genomes with 20 resequencing accessions revealed molecular footprints of artificial selection, providing us with a list of candidate domestication genes. We also found that dosage compensation effect of tandem duplication genes probably contributed to the pungent diversification in pepper. The Capsicum reference genome provides crucial information for the study of not only the evolution of the pepper genome but also, the Solanaceae family, and it will facilitate the establishment of more effective pepper breeding programs.
ESTHER : Qin_2014_Proc.Natl.Acad.Sci.U.S.A_111_5135
PubMedSearch : Qin_2014_Proc.Natl.Acad.Sci.U.S.A_111_5135
PubMedID: 24591624
Gene_locus related to this paper: capch-q75qh4 , capan-a0a1u8fuf5 , capan-a0a1u8gmz3 , capan-a0a1u8f879 , capan-a0a1u8ftr2 , capan-a0a1u8g8s6

Title : Molecular Basis of the General Base Catalysis of an alpha\/beta-Hydrolase Catalytic Triad - Sun_2014_J.Biol.Chem_289_15867
Author(s) : Sun Y , Yin S , Feng Y , Li J , Zhou J , Liu C , Zhu G , Guo Z
Ref : Journal of Biological Chemistry , 289 :15867 , 2014
Abstract : The serine-histidine-aspartate triad is well known for its covalent, nucleophilic catalysis in a diverse array of enzymatic transformations. Here we show that its nucleophilicity is shielded and its catalytic role is limited to being a specific general base by an open-closed conformational change in the catalysis of (1R,6R)-2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase (or MenH), a typical alpha/beta-hydrolase fold enzyme in the vitamin K biosynthetic pathway. This enzyme is found to adopt an open conformation without a functional triad in its ligand-free form and a closed conformation with a fully functional catalytic triad in the presence of its reaction product. The open-to-closed conformational transition involves movement of half of the alpha-helical cap domain, which causes extensive structural changes in the alpha/beta-domain and forces the side chain of the triad histidine to adopt an energetically disfavored gauche conformation to form the functional triad. NMR analysis shows that the inactive open conformation without a triad prevails in ligand-free solution and is converted to the closed conformation with a properly formed triad by the reaction product. Mutation of the residues crucial to this open-closed transition either greatly decreases or completely eliminates the enzyme activity, supporting an important catalytic role for the structural change. These findings suggest that the open-closed conformational change tightly couples formation of the catalytic triad to substrate binding to enhance the substrate specificities and simultaneously shield the nucleophilicity of the triad, thus allowing it to expand its catalytic power beyond the nucleophilic catalysis.
ESTHER : Sun_2014_J.Biol.Chem_289_15867
PubMedSearch : Sun_2014_J.Biol.Chem_289_15867
PubMedID: 24737327
Gene_locus related to this paper: ecoli-YFBB

Title : A Francisella virulence factor catalyses an essential reaction of biotin synthesis - Feng_2014_Mol.Microbiol_91_300
Author(s) : Feng Y , Napier BA , Manandhar M , Henke SK , Weiss DS , Cronan JE
Ref : Molecular Microbiology , 91 :300 , 2014
Abstract : We recently identified a gene (FTN_0818) required for Francisella virulence that seemed likely involved in biotin metabolism. However, the molecular function of this virulence determinant was unclear. Here we show that this protein named BioJ is the enzyme of the biotin biosynthesis pathway that determines the chain length of the biotin valeryl side-chain. Expression of bioJ allows growth of an Escherichia coli bioH strain on biotin-free medium, indicating functional equivalence of BioJ to the paradigm pimeloyl-ACP methyl ester carboxyl-esterase, BioH. BioJ was purified to homogeneity, shown to be monomeric and capable of hydrolysis of its physiological substrate methyl pimeloyl-ACP to pimeloyl-ACP, the precursor required to begin formation of the fused heterocyclic rings of biotin. Phylogenetic analyses confirmed that distinct from BioH, BioJ represents a novel subclade of the alpha/beta-hydrolase family. Structure-guided mapping combined with site-directed mutagenesis revealed that the BioJ catalytic triad consists of Ser151, Asp248 and His278, all of which are essential for activity and virulence. The biotin synthesis pathway was reconstituted reaction in vitro and the physiological role of BioJ directly assayed. To the best of our knowledge, these data represent further evidence linking biotin synthesis to bacterial virulence.
ESTHER : Feng_2014_Mol.Microbiol_91_300
PubMedSearch : Feng_2014_Mol.Microbiol_91_300
PubMedID: 24313380
Gene_locus related to this paper: 9gamm-BioJ , fratt-q5nga8

Title : Genome and transcriptome analysis of the fungal pathogen Fusarium oxysporum f. sp. cubense causing banana vascular wilt disease - Guo_2014_PLoS.One_9_e95543
Author(s) : Guo L , Han L , Yang L , Zeng H , Fan D , Zhu Y , Feng Y , Wang G , Peng C , Jiang X , Zhou D , Ni P , Liang C , Liu L , Wang J , Mao C , Fang X , Peng M , Huang J
Ref : PLoS ONE , 9 :e95543 , 2014
Abstract : BACKGROUND: The asexual fungus Fusarium oxysporum f. sp. cubense (Foc) causing vascular wilt disease is one of the most devastating pathogens of banana (Musa spp.). To understand the molecular underpinning of pathogenicity in Foc, the genomes and transcriptomes of two Foc isolates were sequenced. METHODOLOGY/PRINCIPAL FINDINGS: Genome analysis revealed that the genome structures of race 1 and race 4 isolates were highly syntenic with those of F. oxysporum f. sp. lycopersici strain Fol4287. A large number of putative virulence associated genes were identified in both Foc genomes, including genes putatively involved in root attachment, cell degradation, detoxification of toxin, transport, secondary metabolites biosynthesis and signal transductions. Importantly, relative to the Foc race 1 isolate (Foc1), the Foc race 4 isolate (Foc4) has evolved with some expanded gene families of transporters and transcription factors for transport of toxins and nutrients that may facilitate its ability to adapt to host environments and contribute to pathogenicity to banana. Transcriptome analysis disclosed a significant difference in transcriptional responses between Foc1 and Foc4 at 48 h post inoculation to the banana 'Brazil' in comparison with the vegetative growth stage. Of particular note, more virulence-associated genes were up regulated in Foc4 than in Foc1. Several signaling pathways like the mitogen-activated protein kinase Fmk1 mediated invasion growth pathway, the FGA1-mediated G protein signaling pathway and a pathogenicity associated two-component system were activated in Foc4 rather than in Foc1. Together, these differences in gene content and transcription response between Foc1 and Foc4 might account for variation in their virulence during infection of the banana variety 'Brazil'. CONCLUSIONS/SIGNIFICANCE: Foc genome sequences will facilitate us to identify pathogenicity mechanism involved in the banana vascular wilt disease development. These will thus advance us develop effective methods for managing the banana vascular wilt disease, including improvement of disease resistance in banana.
ESTHER : Guo_2014_PLoS.One_9_e95543
PubMedSearch : Guo_2014_PLoS.One_9_e95543
PubMedID: 24743270
Gene_locus related to this paper: fusox-w9hvf0 , fusox-x0d9n6

Title : Differential efficiency in exogenous DNA acquisition among closely related Salmonella strains: implications in bacterial speciation - Bao_2014_BMC.Microbiol_14_157
Author(s) : Bao HX , Tang L , Yu L , Wang XY , Li Y , Deng X , Li YG , Li A , Zhu DL , Johnston RN , Liu GR , Feng Y , Liu SL
Ref : BMC Microbiol , 14 :157 , 2014
Abstract : BACKGROUND: Acquisition of exogenous genetic material is a key event in bacterial speciation. It seems reasonable to assume that recombination of the incoming DNA into genome would be more efficient with higher levels of relatedness between the DNA donor and recipient. If so, bacterial speciation would be a smooth process, leading to a continuous spectrum of genomic divergence of bacteria, which, however, is not the case as shown by recent findings. The goal of this study was todetermine if DNA transfer efficiency is correlated with the levels of sequence identity.
RESULTS: To compare the relative efficiency of exogenous DNA acquisition among closely related bacteria, we carried out phage-mediated transduction and plasmid-mediated transformation in representative Salmonella strains with different levels of relatedness. We found that the efficiency was remarkably variable even among genetically almost identical bacteria. Although there was a general tendency that more closely related DNA donor-recipient pairs had higher transduction efficiency, transformation efficiency exhibited over a thousand times difference among the closely related Salmonella strains. CONCLUSION: DNA acquisition efficiency is greatly variable among bacteria that have as high as over 99% identical genetic background, suggesting that bacterial speciation involves highly complex processes affected not only by whether beneficial exogenous DNA may exist in the environment but also the "readiness" of the bacteria to accept it.
ESTHER : Bao_2014_BMC.Microbiol_14_157
PubMedSearch : Bao_2014_BMC.Microbiol_14_157
PubMedID: 24928416
Gene_locus related to this paper: salbn-a0a068cr75

Title : Enhanced Enzyme Kinetic Stability by Increasing Rigidity within the Active Site - Xie_2014_J.Biol.Chem_289_7994
Author(s) : Xie Y , An J , Yang G , Wu G , Zhang Y , Cui L , Feng Y
Ref : Journal of Biological Chemistry , 289 :7994 , 2014
Abstract : Enzyme stability is an important issue for protein engineers. Understanding how rigidity in the active site affects protein kinetic stability will provide new insight into enzyme stabilization. In this study, we demonstrated enhanced kinetic stability of Candida antarctica lipase B (CalB) by mutating the structurally flexible residues within the active site. Six residues within 10 A of the catalytic Ser(105) residue with a high B factor were selected for iterative saturation mutagenesis. After screening 2200 colonies, we obtained the D223G/L278M mutant, which exhibited a 13-fold increase in half-life at 48 degrees C and a 12 degrees C higher T50(15), the temperature at which enzyme activity is reduced to 50% after a 15-min heat treatment. Further characterization showed that global unfolding resistance against both thermal and chemical denaturation also improved. Analysis of the crystal structures of wild-type CalB and the D223G/L278M mutant revealed that the latter formed an extra main chain hydrogen bond network with seven structurally coupled residues within the flexible alpha10 helix that are primarily involved in forming the active site. Further investigation of the relative B factor profile and molecular dynamics simulation confirmed that the enhanced rigidity decreased fluctuation of the active site residues at high temperature. These results indicate that enhancing the rigidity of the flexible segment within the active site may provide an efficient method for improving enzyme kinetic stability.
ESTHER : Xie_2014_J.Biol.Chem_289_7994
PubMedSearch : Xie_2014_J.Biol.Chem_289_7994
PubMedID: 24448805
Gene_locus related to this paper: canar-LipB

Title : Comparative analysis of bat genomes provides insight into the evolution of flight and immunity - Zhang_2013_Science_339_456
Author(s) : Zhang G , Cowled C , Shi Z , Huang Z , Bishop-Lilly KA , Fang X , Wynne JW , Xiong Z , Baker ML , Zhao W , Tachedjian M , Zhu Y , Zhou P , Jiang X , Ng J , Yang L , Wu L , Xiao J , Feng Y , Chen Y , Sun X , Zhang Y , Marsh GA , Crameri G , Broder CC , Frey KG , Wang LF , Wang J
Ref : Science , 339 :456 , 2013
Abstract : Bats are the only mammals capable of sustained flight and are notorious reservoir hosts for some of the world's most highly pathogenic viruses, including Nipah, Hendra, Ebola, and severe acute respiratory syndrome (SARS). To identify genetic changes associated with the development of bat-specific traits, we performed whole-genome sequencing and comparative analyses of two distantly related species, fruit bat Pteropus alecto and insectivorous bat Myotis davidii. We discovered an unexpected concentration of positively selected genes in the DNA damage checkpoint and nuclear factor kappaB pathways that may be related to the origin of flight, as well as expansion and contraction of important gene families. Comparison of bat genomes with other mammalian species has provided new insights into bat biology and evolution.
ESTHER : Zhang_2013_Science_339_456
PubMedSearch : Zhang_2013_Science_339_456
PubMedID: 23258410
Gene_locus related to this paper: myods-l5mij9 , pteal-l5k8f5 , pteal-l5kjy3 , pteal-l5k6f0 , pteal-l5kxe2 , myods-l5m0a8 , myods-l5lvb4 , pteal-l5k7h7 , myods-l5lm42 , pteal-l5jz73 , pteal-l5kvh1.1 , pteal-l5kvh1.2 , pteal-l5kw21 , myods-l5lug5 , pteal-l5kv18 , myods-l5lbf8 , pteal-l5kwh0 , myods-l5lfh8 , myods-l5lfr7 , myods-l5lu20 , pteal-l5jzi4 , pteal-l5kib7 , pteal-l5kyq5 , myods-l5lf36 , myods-l5lnh7 , myods-l5lu25 , pteal-l5k0u1 , pteal-l5k2g6 , pteal-l5l3r3 , myods-l5mdx5 , pteal-l5k220 , myolu-g1pdp2 , pteal-l5l5n3 , pteal-l5k1s7 , myolu-g1nth4 , pteal-l5l7w7 , pteal-l5l537 , myods-l5lwe4 , pteal-l5klr9 , pteal-l5k670 , pteal-l5jr94 , pteal-l5kvb4 , myolu-g1q4e3 , pteal-l5jrl1

Title : Genome analysis reveals insights into physiology and longevity of the Brandt's bat Myotis brandtii - Seim_2013_Nat.Commun_4_2212
Author(s) : Seim I , Fang X , Xiong Z , Lobanov AV , Huang Z , Ma S , Feng Y , Turanov AA , Zhu Y , Lenz TL , Gerashchenko MV , Fan D , Hee Yim S , Yao X , Jordan D , Xiong Y , Ma Y , Lyapunov AN , Chen G , Kulakova OI , Sun Y , Lee SG , Bronson RT , Moskalev AA , Sunyaev SR , Zhang G , Krogh A , Wang J , Gladyshev VN
Ref : Nat Commun , 4 :2212 , 2013
Abstract : Bats account for one-fifth of mammalian species, are the only mammals with powered flight, and are among the few animals that echolocate. The insect-eating Brandt's bat (Myotis brandtii) is the longest-lived bat species known to date (lifespan exceeds 40 years) and, at 4-8 g adult body weight, is the most extreme mammal with regard to disparity between body mass and longevity. Here we report sequencing and analysis of the Brandt's bat genome and transcriptome, which suggest adaptations consistent with echolocation and hibernation, as well as altered metabolism, reproduction and visual function. Unique sequence changes in growth hormone and insulin-like growth factor 1 receptors are also observed. The data suggest that an altered growth hormone/insulin-like growth factor 1 axis, which may be common to other long-lived bat species, together with adaptations such as hibernation and low reproductive rate, contribute to the exceptional lifespan of the Brandt's bat.
ESTHER : Seim_2013_Nat.Commun_4_2212
PubMedSearch : Seim_2013_Nat.Commun_4_2212
PubMedID: 23962925
Gene_locus related to this paper: myobr-s7mf99 , myobr-s7n4r2 , myobr-s7neb7 , myobr-s7ney7 , myobr-s7n9l2 , myobr-s7nk13 , myobr-s7mh20 , myobr-s7pbt8 , myobr-s7mux2 , myobr-s7mjb5 , myobr-s7n6x5 , myobr-s7nnt6 , myobr-s7n728.2 , myobr-s7n728.3 , myobr-s7n8d2 , myobr-s7nqw0 , myobr-s7mju4 , myolu-g1nth4 , myobr-s7mij5 , myobr-s7pr94 , myolu-g1q4e3 , myolu-g1p353

Title : Role of the NC-loop in catalytic activity and stability in lipase from Fervidobacterium changbaicum - Li_2012_PLoS.One_7_e46881
Author(s) : Li B , Yang G , Wu L , Feng Y
Ref : PLoS ONE , 7 :e46881 , 2012
Abstract : Flexible NC-loops between the catalytic domain and the cap domain of the alpha/beta hydrolase fold enzymes show remarkable diversity in length, sequence, and configuration. Recent investigations have suggested that the NC-loop might be involved in catalysis and substrate recognition in many enzymes from the alpha/beta hydrolase fold superfamily. To foster a deep understanding of its role in catalysis, stability, and divergent evolution, we here systemically investigated the function of the NC-loop (residues 131-151) in a lipase (FClip1) from thermophilic bacterium Fervidobacterium changbaicum by loop deletion, alanine-scanning mutagenesis and site-directed mutagenesis. We found that the upper part of the NC-loop (residues 131-138) was of great importance to enzyme catalysis. Single substitutions in this region could fine-tune the activity of FClip1 as much as 41-fold, and any deletions from this region rendered the enzyme completely inactive. The lower part of the NC-loop (residues 139-151) was capable of enduring extensive deletions without loss of activity. The shortened mutants in this region were found to show both improved activity and increased stability simultaneously. We therefore speculated that the NC-loop, especially the lower part, would be a perfect target for enzyme engineering to optimize the enzymatic properties, and might present a hot zone for the divergent evolution of alpha/beta hydrolases. Our findings may provide an opportunity for better understanding of the mechanism of divergent evolution in the alpha/beta hydrolase fold superfamily, and may also guide the design of novel biocatalysts for industrial applications.
ESTHER : Li_2012_PLoS.One_7_e46881
PubMedSearch : Li_2012_PLoS.One_7_e46881
PubMedID: 23056508
Gene_locus related to this paper: 9them-a1yv97

Title : High yield recombinant expression, characterization and homology modeling of two types of cis-epoxysuccinic acid hydrolases - Cui_2012_Protein.J_31_432
Author(s) : Cui GZ , Wang S , Li Y , Tian YJ , Feng Y , Cui Q
Ref : Protein J , 31 :432 , 2012
Abstract : The cis-epoxysuccinate hydrolases (CESHs), members of epoxide hydrolase, catalyze cis-epoxysuccinic acid hydrolysis to form D: (-)-tartaric acid or L: (+)-tartaric acid which are important chemicals with broad scientific and industrial applications. Two types of CESHs (CESH[D: ] and CESH[L: ], producing D: (-)- and L: (+)-tartaric acids, respectively) have been reported with low yield and complicated purification procedure in previous studies. In this paper, the two CESHs were overexpressed in Escherichia coli using codon-optimized genes. High protein yields by one-step purifications were obtained for both recombinant enzymes. The optimal pH and temperature were measured for both recombinant CESHs, and the properties of recombinant enzymes were similar to native enzymes. Kinetics parameters measured by Lineweaver-Burk plot indicates both enzymes exhibited similar affinity to cis-epoxysuccinic acid, but CESH[L: ] showed much higher catalytic efficiency than CESH[D: ], suggesting that the two CESHs have different catalytic mechanisms. The structures of both CESHs constructed by homology modeling indicated that CESH[L: ] and CESH[D: ] have different structural folds and potential active site residues. CESH[L: ] adopted a typical alpha/beta-hydrolase fold with a cap domain and a core domain, whereas CESH[D: ] possessed a unique TIM barrel fold composed of 8 alpha-helices and 8 beta-strands, and 2 extra short alpha-helices exist on the top and bottom of the barrel, respectively. A divalent metal ion, preferred to be zinc, was found in CESH[D: ], and the ion was proved to be crucial to the enzymatic activity. These results provide structural insight into the different catalytic mechanisms of the two CESHs.
ESTHER : Cui_2012_Protein.J_31_432
PubMedSearch : Cui_2012_Protein.J_31_432
PubMedID: 22592448

Title : The oyster genome reveals stress adaptation and complexity of shell formation - Zhang_2012_Nature_490_49
Author(s) : Zhang G , Fang X , Guo X , Li L , Luo R , Xu F , Yang P , Zhang L , Wang X , Qi H , Xiong Z , Que H , Xie Y , Holland PW , Paps J , Zhu Y , Wu F , Chen Y , Wang J , Peng C , Meng J , Yang L , Liu J , Wen B , Zhang N , Huang Z , Zhu Q , Feng Y , Mount A , Hedgecock D , Xu Z , Liu Y , Domazet-Loso T , Du Y , Sun X , Zhang S , Liu B , Cheng P , Jiang X , Li J , Fan D , Wang W , Fu W , Wang T , Wang B , Zhang J , Peng Z , Li Y , Li N , Chen M , He Y , Tan F , Song X , Zheng Q , Huang R , Yang H , Du X , Chen L , Yang M , Gaffney PM , Wang S , Luo L , She Z , Ming Y , Huang W , Huang B , Zhang Y , Qu T , Ni P , Miao G , Wang Q , Steinberg CE , Wang H , Qian L , Liu X , Yin Y
Ref : Nature , 490 :49 , 2012
Abstract : The Pacific oyster Crassostrea gigas belongs to one of the most species-rich but genomically poorly explored phyla, the Mollusca. Here we report the sequencing and assembly of the oyster genome using short reads and a fosmid-pooling strategy, along with transcriptomes of development and stress response and the proteome of the shell. The oyster genome is highly polymorphic and rich in repetitive sequences, with some transposable elements still actively shaping variation. Transcriptome studies reveal an extensive set of genes responding to environmental stress. The expansion of genes coding for heat shock protein 70 and inhibitors of apoptosis is probably central to the oyster's adaptation to sessile life in the highly stressful intertidal zone. Our analyses also show that shell formation in molluscs is more complex than currently understood and involves extensive participation of cells and their exosomes. The oyster genome sequence fills a void in our understanding of the Lophotrochozoa.
ESTHER : Zhang_2012_Nature_490_49
PubMedSearch : Zhang_2012_Nature_490_49
PubMedID: 22992520
Gene_locus related to this paper: cragi-k1qzk7 , cragi-k1rad0 , cragi-k1p6v9 , cragi-k1pa46 , cragi-k1pga2 , cragi-k1pp63 , cragi-k1pwa8 , cragi-k1q0b1.1 , cragi-k1q0b1.2 , cragi-k1q1h2 , cragi-k1q2z6 , cragi-k1qaj8 , cragi-k1qaw5 , cragi-k1qhl5 , cragi-k1qly1 , cragi-k1qqb1.1 , cragi-k1qqb1.2 , cragi-k1qs61 , cragi-k1qs99 , cragi-k1qwl6 , cragi-k1r068 , cragi-k1r0n3.1 , cragi-k1r0n3.2 , cragi-k1r0r4 , cragi-k1r1i9 , cragi-k1r8q9 , cragi-k1rgi1 , cragi-k1rig4 , cragi-k1s0a7.1 , cragi-k1s0a7.2 , cragi-k1s0a7.3 , cragi-k1q6q0 , cragi-k1rru1 , cragi-k1qfi4 , cragi-k1qvm5 , cragi-k1qq58 , cragi-k1qdc0 , cragi-k1r754 , cragi-k1pje5 , cragi-k1qca6 , cragi-k1qdt5 , cragi-k1qkz7 , cragi-k1rgd2 , cragi-k1puh6 , cragi-k1raz4 , cragi-k1qqj4 , cragi-k1rbs1

Title : Enzyme Promiscuity in the Hormone-Sensitive Lipase Family of Proteins - Manco_2012_Protein.Pept.Lett_19_144
Author(s) : Manco G , Merone L , Porzio E , Feng Y , Mandrich L
Ref : Protein Pept Lett , 19 :144 , 2012
Abstract : The number of enzymes endowed with the capacity to catalyse other reactions than the main, physiological one, a feature that has been called promiscuity, is increasing at a fast pace. Promiscuity is a highly pervasive phenomenon that is present at each level of life complexity. For enzymes, promiscuity encompasses interesting aspects related to their physiological role, evolution and biotechnological applications. Herein, at first we will describe some general aspects of enzyme promiscuity and then we will report some examples from the alpha/beta hydrolase superfamily of proteins, with particular emphasis to the hormone-sensitive lipase family.
ESTHER : Manco_2012_Protein.Pept.Lett_19_144
PubMedSearch : Manco_2012_Protein.Pept.Lett_19_144
PubMedID: 21933124
Gene_locus related to this paper: human-LIPE

Title : Complete genome sequence of Salmonella enterica serovar pullorum RKS5078 - Feng_2012_J.Bacteriol_194_744
Author(s) : Feng Y , Xu HF , Li QH , Zhang SY , Wang CX , Zhu DL , Cao FL , Li YG , Johnston RN , Zhou J , Liu GR , Liu SL
Ref : Journal of Bacteriology , 194 :744 , 2012
Abstract : Salmonella enterica serovar Pullorum is a chicken-adapted pathogen, causing pullorum disease. Its strict host adaptation has been suspected to result in gene decay. To validate this hypothesis and identify the decayed genes, we sequenced the complete genome of S. Pullorum RKS5078. We found 263 pseudogenes in this strain and conducted functional analyses of the decayed genes.
ESTHER : Feng_2012_J.Bacteriol_194_744
PubMedSearch : Feng_2012_J.Bacteriol_194_744
PubMedID: 22247537
Gene_locus related to this paper: salty-STY1441 , salty-YFBB

Title : Alteration of substrate specificities of thermophilic alpha\/beta hydrolases through domain swapping and domain interface optimization - Zhou_2012_Acta.Biochim.Biophys.Sin.(Shanghai)_44_965
Author(s) : Zhou X , Wang H , Zhang Y , Gao L , Feng Y
Ref : Acta Biochim Biophys Sin (Shanghai) , 44 :965 , 2012
Abstract : Protein domain swapping is an efficient way in protein functional evolution in vivo and also has been proved to be an effective strategy to modify the function of the multi-domain proteins in vitro. To explore the potentials of domain swapping for alteration of the enzyme substrate specificities and the structure-function relationship of the homologous proteins, here we constructed two chimeras from a pair of thermophilic members of the alpha/beta hydrolase superfamily by grafting their functional domains to the conserved alpha/beta hydrolase fold domain: a carboxylesterase from Archaeoglobus fulgidus (AFEST) and an acylpeptide hydrolase from Aeropyrum pernix K1 (apAPH) and explored their activities on hydrolyze p-nitrophenyl esters (pNP) with different acyl chain lengths. We took two approaches to reduce the crossover disruptions when creating the chimeras: chose the residue which involved in the least contacts as the splicing site and optimized the newly formed domain interfaces of the chimeras by site-directed mutations. Characterizations of AAM7 and PAR showed that these chimeras inherited the thermophilic property of both parents. In the aspect of substrate specificity, AAM7 and PAR showed highest activity towards short chain length substrate pNPC4 and middle chain length substrate pNPC8, similar to parent AFEST and apAPH, respectively. These results suggested that the substrate-binding domain is the dominant factor on enzyme substrate specificity, and the optimization of the newly formed domain interface is an important guarantee for successful domain swapping of proteins with low-sequence homology.
ESTHER : Zhou_2012_Acta.Biochim.Biophys.Sin.(Shanghai)_44_965
PubMedSearch : Zhou_2012_Acta.Biochim.Biophys.Sin.(Shanghai)_44_965
PubMedID: 23099882

Title : Genome sequences of two multidrug-resistant Acinetobacter baumannii strains isolated from a patient before and after treatment with tigecycline - Hua_2012_J.Bacteriol_194_6979
Author(s) : Hua X , Zhou H , Jiang Y , Feng Y , Chen Q , Ruan Z , Yu Y
Ref : Journal of Bacteriology , 194 :6979 , 2012
Abstract : Acinetobacter baumannii is a Gram-negative bacterium which emerged as a significant nosocomial pathogen worldwide. To investigate the molecular basis of the tigecycline-resistant mechanism, we determined the genome sequences of two multidrug-resistant A. baumannii strains isolated from a patient before and after treatment with tigecycline.
ESTHER : Hua_2012_J.Bacteriol_194_6979
PubMedSearch : Hua_2012_J.Bacteriol_194_6979
PubMedID: 23209232
Gene_locus related to this paper: aciba-f5iht4 , aciba-a0a009wzt4

Title : Fervidobacterium changbaicum Lip1: identification, cloning, and characterization of the thermophilic lipase as a new member of bacterial lipase family V - Cai_2011_Appl.Microbiol.Biotechnol_89_1463
Author(s) : Cai J , Xie Y , Song B , Wang Y , Zhang Z , Feng Y
Ref : Applied Microbiology & Biotechnology , 89 :1463 , 2011
Abstract : A novel lipase gene encoded 315 amino acid residues was obtained using lipase-prospecting primers and genome walking from hyperthermophilic bacterium Fervidobacterium changbaicum CBS-1. Sequence alignment and phylogenetic analysis revealed this novel lipase is a new member of bacterial lipase family V. The recombinant enzyme F. changbaicum lipase 1 (FCLip1) showed maximum activity at 78 degreesC and pH 7.8. It displayed extreme thermostability at 70 degreesC and was also stable across a wide pH range from 6.0 to 12.0. Kinetic study demonstrated FCLip1 preferentially hydrolyzed middle-length acyl chains, especially p-nitrophenyl caprate and tricaprylin. With p-nitrophenyl caprate as a substrate, the enzyme exhibited a K(m) and k(cat) of 4.67 microM and 22.7/s, respectively. In addition, FCLip1 was resistant to various detergents and organic solvents. This enzyme is the first reported thermophilic lipase from bacterial family Thermotogaceae. Its extreme stability with respect to temperature and pH, along with its triglyceride hydrolysis activity, indicate that FCLip1 has high potential for future application.
ESTHER : Cai_2011_Appl.Microbiol.Biotechnol_89_1463
PubMedSearch : Cai_2011_Appl.Microbiol.Biotechnol_89_1463
PubMedID: 21046373
Gene_locus related to this paper: 9them-a1yv97

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

Title : Switch of substrate specificity of hyperthermophilic acylaminoacyl peptidase by combination of protein and solvent engineering - Liu_2011_Protein.Cell_2_497
Author(s) : Liu C , Yang G , Wu L , Tian G , Zhang Z , Feng Y
Ref : Protein Cell , 2 :497 , 2011
Abstract : The inherent evolvability of promiscuous enzymes endows them with great potential to be artificially evolved for novel functions. Previously, we succeeded in transforming a promiscuous acylaminoacyl peptidase (apAAP) from the hyperthermophilic archaeon Aeropyrum pernix K1 into a specific carboxylesterase by making a single mutation. In order to fulfill the urgent requirement of thermostable lipolytic enzymes, in this paper we describe how the substrate preference of apAAP can be further changed from p-nitrophenyl caprylate (pNP-C8) to p-nitrophenyl laurate (pNP-C12) by protein and solvent engineering. After one round of directed evolution and subsequent saturation mutagenesis at selected residues in the active site, three variants with enhanced activity towards pNP-C12 were identified. Additionally, a combined mutant W474V/F488G/R526V/T560W was generated, which had the highest catalytic efficiency (k (cat)/K (m)) for pNP-C12, about 71-fold higher than the wild type. Its activity was further increased by solvent engineering, resulting in an activity enhancement of 280-fold compared with the wild type in the presence of 30% DMSO. The structural basis for the improved activity was studied by substrate docking and molecular dynamics simulation. It was revealed that W474V and F488G mutations caused a significant change in the geometry of the active center, which may facilitate binding and subsequent hydrolysis of bulky substrates. In conclusion, the combination of protein and solvent engineering may be an effective approach to improve the activities of promiscuous enzymes and could be used to create naturally rare hyperthermophilic enzymes.
ESTHER : Liu_2011_Protein.Cell_2_497
PubMedSearch : Liu_2011_Protein.Cell_2_497
PubMedID: 21748600

Title : Gene cloning and characterization of a novel thermophilic esterase from Fervidobacterium nodosum Rt17-B1 - Yu_2010_Acta.Biochim.Biophys.Sin.(Shanghai)_42_288
Author(s) : Yu S , Zheng B , Zhao X , Feng Y
Ref : Acta Biochim Biophys Sin (Shanghai) , 42 :288 , 2010
Abstract : A bioinformatic screening of the genome of the thermophilic bacterium Fervidobacterium nodosum Rt17-B1 for esterhydrolyzing enzymes revealed a putative bacterial esterase (FNE) encoded by Fond_1301 with typical GDSL family motifs. To confirm its putative esterase function, the FNE gene was cloned, functionally expressed in Escherichia coli, and purified to homogeneity. Recombinant FNE exhibited the highest esterase activity of 14,000 U/mg with p-nitrophenyl acetate (pNPC(2)) as substrate. The catalytic efficiency (k(cat)/K(m)) toward p-nitrophenyl acetate (C(2)) was approximately 120-fold higher than toward p-nitrophenyl butyrate (C(4)). No significant esterase activity was observed for the substrates with a chain length > or =C(8). The monomeric enzyme has a molecular mass of 27.5 kDa and exhibits optimal activity around 75 degrees C, at pH 8.5. Its thermostability is relatively high with a half-life of 80 min at 70 degrees C, but less stable compared with some other hyperthermophilic esterases. A structural model was constructed using acetylesterase from Aspergillus aculeatus as a template. The structure showed an alpha/beta-hydrolase fold and indicated the presence of a typical catalytic triad consisting of a serine, aspartate, and histidine, which was verified by site-directed mutagenesis. Sequence analysis showed that FNE was only distantly related to other esterases. A comparison of the conserved motifs shared with GDSL proteins revealed that FNE could be grouped into GDSL family and was further classified as SGNH hydrolase.
ESTHER : Yu_2010_Acta.Biochim.Biophys.Sin.(Shanghai)_42_288
PubMedSearch : Yu_2010_Acta.Biochim.Biophys.Sin.(Shanghai)_42_288
PubMedID: 20383468

Title : Cross-resistance study and biochemical mechanisms of thiamethoxam resistance in B-biotype Bemisia tabaci (Hemiptera: Aleyrodidae) - Feng_2010_Pest.Manag.Sci_66_313
Author(s) : Feng Y , Wu Q , Wang S , Chang X , Xie W , Xu B , Zhang Y
Ref : Pest Manag Sci , 66 :313 , 2010
Abstract : BACKGROUND: B-biotype Bemisia tabaci (Gennadius) has invaded China over the past two decades. To understand the risks and to determine possible mechanisms of resistance to thiamethoxam in B. tabaci, a resistant strain was selected in the laboratory. Cross-resistance and the biochemical mechanisms of thiamethoxam resistance were investigated in the present study. RESULTS: A 66.3-fold thiamethoxam-resistant B. tabaci strain (TH-R) was established after selection for 36 generations. Compared with the susceptible strain (TH-S), the selected TH-R strain showed obvious cross-resistance to imidacloprid (47.3-fold), acetamiprid (35.8-fold), nitenpyram (9.99-fold), abamectin (5.33-fold) and carbosulfan (4.43-fold). No cross-resistance to fipronil, chlorpyrifos or deltamethrin was seen. Piperonyl butoxide (PBO) and triphenyl phosphate (TPP) exhibited significant synergism on thiamethoxam effects in the TH-R strain (3.14- and 2.37-fold respectively). However, diethyl maleate (DEM) did not act synergistically with thiamethoxam. Biochemical assays showed that cytochrome P450 monooxygenase activities increased 1.21- and 1.68-fold respectively, and carboxylesterase activity increased 2.96-fold in the TH-R strain. However, no difference was observed for glutathione S-transferase between the two strains. CONCLUSION: B-biotype B. tabaci develops resistance to thiamethoxam. Cytochrome P450 monooxygenase and carboxylesterase appear to be responsible for the resistance. Reasonable resistance management that avoids the use of cross-resistance insecticides may delay the development of resistance to thiamethoxam in this species.
ESTHER : Feng_2010_Pest.Manag.Sci_66_313
PubMedSearch : Feng_2010_Pest.Manag.Sci_66_313
PubMedID: 19937914

Title : Inhibition of DPP-4 with sitagliptin improves glycemic control and restores islet cell mass and function in a rodent model of type 2 diabetes - Mu_2009_Eur.J.Pharmacol_623_148
Author(s) : Mu J , Petrov A , Eiermann GJ , Woods J , Zhou YP , Li Z , Zycband E , Feng Y , Zhu L , Roy RS , Howard AD , Li C , Thornberry NA , Zhang BB
Ref : European Journal of Pharmacology , 623 :148 , 2009
Abstract : Inhibition of dipeptidyl peptidase-4 (DPP-4) activity has been shown to improve glycemic control in patients with type 2 diabetes by prolonging and potentiating the actions of incretin hormones. This study is designed to determine the effects of the DPP-4 inhibitor sitagliptin on improving islet function in a mouse model of insulin resistance and insulin secretion defects. ICR mice were pre-treated with high fat diet and a low dose of streptozotocin to induce insulin resistance and impaired insulin secretion, respectively. Diabetic mice were treated with sitagliptin or the sulfonylurea agent glipizide as admixture to high fat diet for ten weeks. Sustained reduction of blood glucose, HbA(1c), circulating glucagon and improvement in oral glucose tolerance were observed in mice treated with sitagliptin. In contrast, glipizide improved glycemic control only during the early weeks and to a lesser degree compared to sitagliptin, and had no effect on circulating glucagon levels or glucose tolerance. The improvement in glycemic control in sitagliptin-treated mice was associated with a significant increase in glucose-dependent insulin secretion in both perfused pancreas and isolated islets. Importantly, in contrast to the lack of effect by glipizide, sitagliptin significantly restored beta and alpha cell mass as well as alpha/beta cell ratio. These data indicate that DPP-4 inhibition by sitagliptin provided better overall improvement of glycemic control compared to glipizide in the high fat diet/streptozotocin induced diabetic mouse model. The ability of sitagliptin to enhance islet cell function may offer insight into the potential for disease modification.
ESTHER : Mu_2009_Eur.J.Pharmacol_623_148
PubMedSearch : Mu_2009_Eur.J.Pharmacol_623_148
PubMedID: 19765579

Title : Salmonella paratyphi C: genetic divergence from Salmonella choleraesuis and pathogenic convergence with Salmonella typhi - Liu_2009_PLoS.One_4_e4510
Author(s) : Liu WQ , Feng Y , Wang Y , Zou QH , Chen F , Guo JT , Peng YH , Jin Y , Li YG , Hu SN , Johnston RN , Liu GR , Liu SL
Ref : PLoS ONE , 4 :e4510 , 2009
Abstract : BACKGROUND: Although over 1400 Salmonella serovars cause usually self-limited gastroenteritis in humans, a few, e.g., Salmonella typhi and S. paratyphi C, cause typhoid, a potentially fatal systemic infection. It is not known whether the typhoid agents have evolved from a common ancestor (by divergent processes) or acquired similar pathogenic traits independently (by convergent processes). Comparison of different typhoid agents with non-typhoidal Salmonella lineages will provide excellent models for studies on how similar pathogens might have evolved. METHODOLOGIES/PRINCIPAL FINDINGS: We sequenced a strain of S. paratyphi C, RKS4594, and compared it with previously sequenced Salmonella strains. RKS4594 contains a chromosome of 4,833,080 bp and a plasmid of 55,414 bp. We predicted 4,640 intact coding sequences (4,578 in the chromosome and 62 in the plasmid) and 152 pseudogenes (149 in the chromosome and 3 in the plasmid). RKS4594 shares as many as 4346 of the 4,640 genes with a strain of S. choleraesuis, which is primarily a swine pathogen, but only 4008 genes with another human-adapted typhoid agent, S. typhi. Comparison of 3691 genes shared by all six sequenced Salmonella strains placed S. paratyphi C and S. choleraesuis together at one end, and S. typhi at the opposite end, of the phylogenetic tree, demonstrating separate ancestries of the human-adapted typhoid agents. S. paratyphi C seemed to have suffered enormous selection pressures during its adaptation to man as suggested by the differential nucleotide substitutions and different sets of pseudogenes, between S. paratyphi C and S. choleraesuis. CONCLUSIONS: S. paratyphi C does not share a common ancestor with other human-adapted typhoid agents, supporting the convergent evolution model of the typhoid agents. S. paratyphi C has diverged from a common ancestor with S. choleraesuis by accumulating genomic novelty during adaptation to man.
ESTHER : Liu_2009_PLoS.One_4_e4510
PubMedSearch : Liu_2009_PLoS.One_4_e4510
PubMedID: 19229335
Gene_locus related to this paper: salty-BIOH , salty-FES , salty-IROD , salty-IROE , salty-P74847 , salty-STM0332 , salty-STY1441 , salty-STY2428 , salty-yafa , salty-YBFF , salty-ycfp , salty-YFBB

Title : Glu88 in the non-catalytic domain of acylpeptide hydrolase plays dual roles: charge neutralization for enzymatic activity and formation of salt bridge for thermodynamic stability - Yang_2009_Biochim.Biophys.Acta_1794_94
Author(s) : Yang G , Bai A , Gao L , Zhang Z , Zheng B , Feng Y
Ref : Biochimica & Biophysica Acta , 1794 :94 , 2009
Abstract : Acylpeptide hydrolase of Aeropyrum pernix K1 is composed of a catalytic alpha/beta hydrolase domain and a non-catalytic beta-propeller domain. The Glu88 residue of the propeller domain is highly conserved in the prolyl oligopeptidase family and forms an inter-domain salt bridge with Arg526, a key residue for substrate binding. We have dissected the functions of Glu88 using site-directed mutagenesis, steady-state kinetics analyses, and molecular dynamics simulations. In E88A and E88A/R526K mutants, with a broken inter-domain salt bridge and a positive charge at position 526, catalytic activities for both a peptidase substrate and an esterase substrate were almost abolished. Analysis of the pH dependence of the mutants' reaction kinetics indicates that these mutations lead to changes in the electrostatic environment of the active site, which can be modulated by chloride ions. These findings indicate that the neutralization at position 526 is favorable for the activity of the enzyme, which is also verified by the catalytic behavior of E88A/R526V mutant. All mutants have lower thermodynamic stability than the wild-type. Therefore, Glu88 plays two major roles in the function of the enzyme: neutralizing the positive charge of Arg526, thereby increasing the enzymatic activity, and forming the Glu88-Arg526 salt bridge, thereby stabilizing the protein.
ESTHER : Yang_2009_Biochim.Biophys.Acta_1794_94
PubMedSearch : Yang_2009_Biochim.Biophys.Acta_1794_94
PubMedID: 18930847

Title : Inactivation of dipeptidyl peptidase IV attenuates the virulence of Streptococcus suis serotype 2 that causes streptococcal toxic shock syndrome - Ge_2009_Curr.Microbiol_59_248
Author(s) : Ge J , Feng Y , Ji H , Zhang H , Zheng F , Wang C , Yin Z , Pan X , Tang J
Ref : Curr Microbiol , 59 :248 , 2009
Abstract : Di-peptidyl peptidase IV (DPP IV), originally recognized as CD26 in eukaryotic cells, is distributed widely in microbial pathogens, including Streptococcus suis (S. suis), an emerging zoonotic agent. However, the role of DPP IV in S. suis virulence remains unclear. Here, we identified a dpp IV homologue from highly invasive isolate of S. suis 2 (SS2) causing streptococcal toxic shock syndrome (STSS). Enzymatic assays reproduced its enzymatic activity of dpp IV protein product as a functional DPP IV, and ELISA analysis demonstrated that SS2 DPP IV can interact with human fibronectin. An isogenic SS2 mutant of dpp IV, Delta dpp IV, was obtained by homologous recombination. Experimental animal infection suggested that an inactivation of dpp IV attenuates greatly its high virulence of Chinese virulent strains of SS2. Functional complementation can restore this defect in SS2 pathogenicity. To our knowledge, it may confirm, for the first time, that DPP IV contributes to SS2 virulence.
ESTHER : Ge_2009_Curr.Microbiol_59_248
PubMedSearch : Ge_2009_Curr.Microbiol_59_248
PubMedID: 19484301

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

Title : Saponins (Ginsenosides) from stems and leaves of Panax quinquefolium prevented high-fat diet-induced obesity in mice - Liu_2008_Phytomedicine_15_1140
Author(s) : Liu W , Zheng Y , Han L , Wang H , Saito M , Ling M , Kimura Y , Feng Y
Ref : Phytomedicine , 15 :1140 , 2008
Abstract : The present study was performed to clarify whether the crude saponins from stems and leaves of Panax quinquefolium inhibited lipase activity in vitro, and prevented obesity induced in mice by feeding a high-fat diet for 8 weeks. For in vitro experiments, assay for the inhibitory effects of saponins from stems and leaves of Panax quinquefolium on pancreatic lipase activity was performed by measuring the rate of release of oleic acid from triolein. For in vivo experiments, female ICR mice were fed a high-fat diet with or without saponins from stems and leaves of Panax quinquefolium for 8 weeks. The crude saponins inhibited pancreatic lipase activity in vitro. Furthermore, crude saponins (lg/kg body weight) inhibited the elevations of plasma triacylglycerol in rats administered the oral lipid emulsion tolerance test. In addition, long-term administration of crude saponins, the parametrial adipose tissue weight was decreased by feeding a high-fat diet containing l% or 3% crude saponins compared to those of high-fat diet group. It is demonstrated that the anti-obesity effects of the crude saponins from stems and leaves of Panax quinquefolium in high-fat diet-treated mice may be due to the inhibition of intestinal absorption of dietary fat by ginsenosides Rc, Rb(1) and Rb(2).
ESTHER : Liu_2008_Phytomedicine_15_1140
PubMedSearch : Liu_2008_Phytomedicine_15_1140
PubMedID: 18768305

Title : A glimpse of streptococcal toxic shock syndrome from comparative genomics of S. suis 2 Chinese isolates - Chen_2007_PLoS.One_2_e315
Author(s) : Chen C , Tang J , Dong W , Wang C , Feng Y , Wang J , Zheng F , Pan X , Liu D , Li M , Song Y , Zhu X , Sun H , Feng T , Guo Z , Ju A , Ge J , Dong Y , Sun W , Jiang Y , Yan J , Yang H , Wang X , Gao GF , Yang R , Yu J
Ref : PLoS ONE , 2 :e315 , 2007
Abstract : BACKGROUND: Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen, causing more than 200 cases of severe human infection worldwide, with the hallmarks of meningitis, septicemia, arthritis, etc. Very recently, SS2 has been recognized as an etiological agent for streptococcal toxic shock syndrome (STSS), which was originally associated with Streptococcus pyogenes (GAS) in Streptococci. However, the molecular mechanisms underlying STSS are poorly understood. METHODS AND FINDINGS: To elucidate the genetic determinants of STSS caused by SS2, whole genome sequencing of 3 different Chinese SS2 strains was undertaken. Comparative genomics accompanied by several lines of experiments, including experimental animal infection, PCR assay, and expression analysis, were utilized to further dissect a candidate pathogenicity island (PAI). Here we show, for the first time, a novel molecular insight into Chinese isolates of highly invasive SS2, which caused two large-scale human STSS outbreaks in China. A candidate PAI of approximately 89 kb in length, which is designated 89K and specific for Chinese SS2 virulent isolates, was investigated at the genomic level. It shares the universal properties of PAIs such as distinct GC content, consistent with its pivotal role in STSS and high virulence. CONCLUSIONS: To our knowledge, this is the first PAI candidate from S. suis worldwide. Our finding thus sheds light on STSS triggered by SS2 at the genomic level, facilitates further understanding of its pathogenesis and points to directions of development on some effective strategies to combat highly pathogenic SS2 infections.
ESTHER : Chen_2007_PLoS.One_2_e315
PubMedSearch : Chen_2007_PLoS.One_2_e315
PubMedID: 17375201
Gene_locus related to this paper: strsu-a4vws4 , strsu-q302y4 , strsy-a4vus4 , strsy-a4vwf6

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

Title : Chronic inhibition of dipeptidyl peptidase-4 with a sitagliptin analog preserves pancreatic beta-cell mass and function in a rodent model of type 2 diabetes - Mu_2006_Diabetes_55_1695
Author(s) : Mu J , Woods J , Zhou YP , Roy RS , Li Z , Zycband E , Feng Y , Zhu L , Li C , Howard AD , Moller DE , Thornberry NA , Zhang BB
Ref : Diabetes , 55 :1695 , 2006
Abstract : Inhibitors of dipeptidyl peptidase-4 (DPP-4), a key regulator of the actions of incretin hormones, exert antihyperglycemic effects in type 2 diabetic patients. A major unanswered question concerns the potential ability of DPP-4 inhibition to have beneficial disease-modifying effects, specifically to attenuate loss of pancreatic beta-cell mass and function. Here, we investigated the effects of a potent and selective DPP-4 inhibitor, an analog of sitagliptin (des-fluoro-sitagliptin), on glycemic control and pancreatic beta-cell mass and function in a mouse model with defects in insulin sensitivity and secretion, namely high-fat diet (HFD) streptozotocin (STZ)-induced diabetic mice. Significant and dose-dependent correction of postprandial and fasting hyperglycemia, HbA(1c), and plasma triglyceride and free fatty acid levels were observed in HFD/STZ mice following 2-3 months of chronic therapy. Treatment with des-fluoro-sitagliptin dose dependently increased the number of insulin-positive beta-cells in islets, leading to the normalization of beta-cell mass and beta-cell-to-alpha-cell ratio. In addition, treatment of mice with des-fluoro-sitagliptin, but not glipizide, significantly increased islet insulin content and improved glucose-stimulated insulin secretion in isolated islets. These findings suggest that DPP-4 inhibitors may offer long-lasting efficacy in the treatment of type 2 diabetes by modifying the courses of the disease.
ESTHER : Mu_2006_Diabetes_55_1695
PubMedSearch : Mu_2006_Diabetes_55_1695
PubMedID: 16731832

Title : Discrimination of esterase and peptidase activities of acylaminoacyl peptidase from hyperthermophilic Aeropyrum pernix K1 by a single mutation - Wang_2006_J.Biol.Chem_281_18618
Author(s) : Wang Q , Yang G , Liu Y , Feng Y
Ref : Journal of Biological Chemistry , 281 :18618 , 2006
Abstract : It has been shown that highly conserved residues that form crucial structural elements of the catalytic apparatus may be used to account for the evolutionary history of enzymes. Using saturation mutagenesis, we investigated the role of a conserved residue (Arg(526)) at the active site of acylaminoacyl peptidase from hyperthermophilic Aeropyrum pernix K1 in substrate discrimination and catalytic mechanism. This enzyme has both peptidase and esterase activities. The esterase activity of the wild-type enzyme with p-nitrophenyl caprylate as substrate is approximately 7 times higher than the peptidase activity with Ac-Leu-p-nitroanilide as substrate. However, with the same substrates, this difference was increased to approximately 150-fold for mutant R526V. A more dramatic effect occurred with mutant R526E, which essentially completely abolished the peptidase activity but decreased the esterase activity only by a factor of 2, leading to a 785-fold difference in the enzyme activities. These results provide rare examples that illustrate how enzymes can be evolved to discriminate their substrates by a single mutation. The possible structural and energetic effects of the mutations on k(cat) and K(m) of the enzyme were discussed based on molecular dynamics simulation studies.
ESTHER : Wang_2006_J.Biol.Chem_281_18618
PubMedSearch : Wang_2006_J.Biol.Chem_281_18618
PubMedID: 16670095
Gene_locus related to this paper: aerpe-APE1547

Title : Overexpression and characterization of a lipase from Bacillus subtilis - Ma_2006_Protein.Expr.Purif_45_22
Author(s) : Ma J , Zhang Z , Wang B , Kong X , Wang Y , Cao S , Feng Y
Ref : Protein Expr Purif , 45 :22 , 2006
Abstract : A novel plasmid, pBSR2, was constructed by incorporating a strong lipase promoter and a terminator into the original pBD64. A mature lipase gene from Bacillus subtilis strain IFFI10210, an existing strain for lipase expression, was cloned into the plasmid pBSR2 and transformed into B. subtilis A.S.1.1655. Thus, an overexpression strain, BSL2, was obtained. The yield of lipase is about 8.6 mg protein/g of wet weight of cell mass and 100-fold higher than that in B. subtilis strain IFFI10210. The recombinant lipase was purified in a three-step procedure involving ammonium sulfate fractionation, ion exchange, and gel filtration chromatography. Characterizations of the purified enzyme revealed a molecular mass of 24 kDa in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, maximum activity at 43 degrees C and pH 8.5 for hydrolysis of p-nitrophenyl caprylate. The values of Km and Vm were found to be 0.37 mM and 303 micromol mg-1 min-1, respectively. The substrate specificity study showed that p-nitrophenyl caprylate is a preference of the enzyme. The metal ions Ca2+, K+, and Mg2+ can activate the lipase, whereas Fe2+, Cu2+, and Co2+ inhibited it. The activity of the lipase can be increased about 48% by sodium taurocholate at the concentration of 7 mM and inhibited at concentrations over 10 mM.
ESTHER : Ma_2006_Protein.Expr.Purif_45_22
PubMedSearch : Ma_2006_Protein.Expr.Purif_45_22
PubMedID: 16039141

Title : Prolylcarboxypeptidase gene, chronic hypertension, and risk of preeclampsia - Wang_2006_Am.J.Obstet.Gynecol_195_162
Author(s) : Wang L , Feng Y , Zhang Y , Zhou H , Jiang S , Niu T , Wei LJ , Xu X , Wang X
Ref : Am J Obstet Gynecol , 195 :162 , 2006
Abstract : OBJECTIVE: Renin-angiotensin System is essential for the homeostasis of blood pressure in humans. The roles of renin-angiotensin system gene polymorphisms including angiotensinogen, angiotensin-converting enzyme, renin and angiotensin II receptor, type 1 genes in the pathogenesis of preeclampsia have been extensively studied, but most association studies produced either negative or inconsistent results. Prolylcarboxypeptidase encodes a lysosomal enzyme and is a regulator for both renin-angiotensin system and the kallikrein-kinin system. There is no published study on prolylcarboxypeptidase gene and preeclampsia. STUDY DESIGN: We investigated the independent and joint association of five polymorphisms in angiotensinogen, angiotensin-converting enzyme, and prolylcarboxypeptidase gene and chronic hypertension with the risk of preeclampsia in 125 preeclamptic and 1040 non-preeclamptic black women enrolled at the Boston Medical Center. We used logistic regression models to estimate the odds ratios of risk for preeclampsia associated with each gene polymorphism and its joint association with chronic hypertension. RESULTS: No association was found in four polymorphisms in angiotensinogen and angiotensin-converting enzyme. Prolylcarboxypeptidase E112D (rs2298668) D allele along and jointly with chronic hypertension were associated with a significantly increased risk of preeclampsia. Compared to women with homozygous EE genotype and without chronic hypertension, higher risks of preeclampsia were observed in DD women without chronic hypertension (OR = 3.7, 95% CI, 1.2 - 12.4) and EE women with chronic hypertension (OR = 9.1, 95% CI: 4.7 - 17.6). Women with both D allele and chronic hypertension had the highest risk (OR = 158, 95% CI, 25-infinite). This finding was validated in an independent sample of 1,015 non-black women. We further compared the prolylcarboxypeptidase transcript levels in peripheral blood cells of 23 preeclamptic (30% with chronic hypertension) and 51 non-preeclamptic (6% with chronic hypertension) women 2 - 3 days after delivery. The PRCP transcript levels were lower in ED/DD women than in EE woman (P = .03) and lower in preeclamptic women than in non-preeclamptic women (P = .007). CONCLUSION: Our data showed that prolylcarboxypeptidase D allele coupled with chronic hypertension was associated with a significantly increased risk of preeclampsia in both black and non-black women. Gene expression assays lent further support for the functional significance of prolylcarboxypeptidase in the etiology of preeclampsia.
ESTHER : Wang_2006_Am.J.Obstet.Gynecol_195_162
PubMedSearch : Wang_2006_Am.J.Obstet.Gynecol_195_162
PubMedID: 16681991
Gene_locus related to this paper: human-PRCP

Title : [Directed evolution of Thermophilic esterase from the archaeon Aeropyrum pemix K1] - Wang_2006_Wei.Sheng.Wu.Xue.Bao_46_259
Author(s) : Wang QY , Yang GY , Liu YL , Wang YP , Feng Y
Ref : Wei Sheng Wu Xue Bao , 46 :259 , 2006
Abstract : Thermophilic esterase (APE1547) from Aeropyrum pernix K1 was subjected to error-prone PCR (epPCR) to enhance activity. For the screening of mutants, an efficient and reliable assay suitable for high throughput screening was developed based on the enzyme thermostability. Two successive rounds of random mutagenesis by epPCR resulted in a four amino acid substitution variant M020 with significantly increased activity (six-fold under the screening condition. Further assay for the purified enzymes showed that the mutant possess 1.5-fold higher specific activity and nearly 4-fold higher expressed level than the wild-type. The mutant has an optimal activity at pH 8.5, corresponding to an alkaline shift of 0.5 pH unit compared to the wild type. The structure analysis suggests that R526S may contribute to the enhanced activity and the shift of pKi.
ESTHER : Wang_2006_Wei.Sheng.Wu.Xue.Bao_46_259
PubMedSearch : Wang_2006_Wei.Sheng.Wu.Xue.Bao_46_259
PubMedID: 16736588

Title : Transcriptional activation of the carboxylesterase 2 gene by the p53 pathway - Choi_2006_Cancer.Biol.Ther_5_1450
Author(s) : Choi W , Cogdell D , Feng Y , Hamilton SR , Zhang W
Ref : Cancer Biol Ther , 5 :1450 , 2006
Abstract : The p53 tumor suppressor is an important regulator of cellular response to chemotherapeutic agents by virtue of the protein's ability, upon activation by phosphorylation, to transcriptionally activate a number of genes involved in cell proliferation, apoptosis, and metabolism. Transcriptome analysis following introduction of a constitutively active form of p53 (p53T18D/S20D) into colon carcinoma cell lines identified transcriptional activation of the carboxylesterase 2 (CES-2) gene, which is involved in drug metabolism. We examined whether p53 activated by the DNA-damaging drug 5-fluorouracil (5-FU) also induces CES-2 expression. Our experiments showed that 5-FU induced CES-2 expression in two colon carcinoma cell lines that express wild-type p53 (HCT116 p53(+/+) and RKO) but not in five lines that are p53-null (HCT116 p53(-/- )) or express mutated p53 (HT29, KM12C, KM12SM, and KM12L4A). Sequence analysis revealed a putative p53-binding element in the first intron of CES-2 that differed from consensus by one nucleotide. A reporter gene assay showed that the luciferase construct with the p53-binding element responded to 5-FU treatment, whereas the reporter construct without the binding element did not. Chromatin immunoprecipitation assay confirmed that p53 bound the CES-2 fragment containing the p53-binding element after 5-FU treatment, whereas p21 binding to p53 was present with or without chemotherapy. Knockdown of expression of CES-2 and p53 by small interference RNA in RKO and HCT116 p53(+/+) cells attenuated the anti-proliferation effects of CPT11. These results taken together show that activated p53 directly regulates CES-2 expression via a p53-binding site, representing a novel mechanism through which the p53 pathway modulates drug metabolism. In addition, the degree of homology in the p53-binding element may determine the strength of p53 regulation.
ESTHER : Choi_2006_Cancer.Biol.Ther_5_1450
PubMedSearch : Choi_2006_Cancer.Biol.Ther_5_1450
PubMedID: 16963839

Title : Expression, purification and crystal structure of a truncated acylpeptide hydrolase from Aeropyrum pernix K1 - Zhang_2005_Acta.Biochim.Biophys.Sin.(Shanghai)_37_613
Author(s) : Zhang HF , Zheng BS , Peng Y , Lou ZY , Feng Y , Rao ZH
Ref : Acta Biochim Biophys Sin (Shanghai) , 37 :613 , 2005
Abstract : Acylpeptide hydrolase (APH) catalyzes the N-terminal hydrolysis of Nalpha-acylpeptides to release Nalpha-acylated amino acids. The crystal structure of recombinant APH from the thermophilic archaeon Aeropyrum pernix K1 (apAPH) was reported recently to be at a resolution of 2.1 Angstrom; using X-ray diffraction. A truncated mutant of apAPH that lacks the first short alpha-helix at the N-terminal, apAPH-delta(1-21), was cloned, expressed, characterized and crystallized. Data from biochemical experiments indicate that the optimum temperature of apAPH is decreased by 15 degrees C with the deletion of the N-terminal alpha-helix. However, the enzyme activity at the optimal temperature does not change. It suggests that this N-terminal alpha-helix is essential for thermostability. Here, the crystal structure of apAPH-delta(1-21) has been determined by molecular replacement to 2.5 Angstrom;. A comparison between the two structures suggests a difference in thermostability, and it can be concluded that by adding or deleting a linking structure (located over different domains), the stability or even the activity of an enzyme can be modified.
ESTHER : Zhang_2005_Acta.Biochim.Biophys.Sin.(Shanghai)_37_613
PubMedSearch : Zhang_2005_Acta.Biochim.Biophys.Sin.(Shanghai)_37_613
PubMedID: 16143816
Gene_locus related to this paper: aerpe-APE1547

Title : [Genomic analysis of serine carboxypeptidase-like protein family of Arabidopsis thaliana] - Feng_2005_Yi.Chuan.Xue.Bao_32_864
Author(s) : Feng Y , Liu QP , Jia J , Xue QZ
Ref : Yi Chuan Xue Bao , 32 :864 , 2005
Abstract : Based on hidden Markov models (HMM), the paper utilized reported SCP (Serine Carboxypeptidases) protein sequences as datasets to build HMM profile. To search Arabidopsis thaliana whole proteome,and identified 54 SCPL (Serine Carboxypeptidase-Like) proteins coding genes. The intron-exon structure, the chromosome mapping and the characteristic of coded protein sequences of those 54 putative genes were analyzed in details, revealing seven gene clusters probably resulted from recent gene duplication. This implied that a remarkable number of Arabidopsis thaliana SCPL genes are harboring alternative splice sites. Phylogenetics evolution analysis suggested 88.9% proteins encoded by Arabidopsis genes belong to two string subfamily of carboxypeptidase, I or II, while only 11.1% proteins fall into single string carboxypeptidase III subfamily. Our results indicated besides the facts that all enzymes of this family contained a central catalytic domain of unique topology and three dimensional structure designated as "alpha/beta hydrolase fold", the DNA and their encoded protein sequences also gave clues to phylogentics studies.
ESTHER : Feng_2005_Yi.Chuan.Xue.Bao_32_864
PubMedSearch : Feng_2005_Yi.Chuan.Xue.Bao_32_864
PubMedID: 16231742

Title : Crystal Structure of an Acylpeptide Hydrolase\/Esterase from Aeropyrum pernix K1. - Bartlam_2004_Structure.(Camb)_12_1481
Author(s) : Bartlam M , Wang G , Yang H , Gao R , Zhao X , Xie G , Cao S , Feng Y , Rao Z
Ref : Structure(Camb) , 12 :1481 , 2004
Abstract : Acylpeptide hydrolases (APH; also known as acylamino acid releasing enzyme) catalyze the removal of an N-acylated amino acid from blocked peptides. The crystal structure of an APH from the thermophilic archaeon Aeropyrum pernix K1 to 2.1 A resolution confirms it to be a member of the prolyl oligopeptidase family of serine proteases. The structure of apAPH is a symmetric homodimer with each subunit comprised of two domains. The N-terminal domain is a regular seven-bladed beta-propeller, while the C-terminal domain has a canonical alpha/beta hydrolase fold and includes the active site and a conserved Ser445-Asp524-His556 catalytic triad. The complex structure of apAPH with an organophosphorus substrate, p-nitrophenyl phosphate, has also been determined. The complex structure unambiguously maps out the substrate binding pocket and provides a basis for substrate recognition by apAPH. A conserved mechanism for protein degradation from archaea to mammals is suggested by the structural features of apAPH.
ESTHER : Bartlam_2004_Structure.(Camb)_12_1481
PubMedSearch : Bartlam_2004_Structure.(Camb)_12_1481
PubMedID: 15296741
Gene_locus related to this paper: aerpe-APE1547

Title : A common haplotype of the nicotine acetylcholine receptor alpha 4 subunit gene is associated with vulnerability to nicotine addiction in men - Feng_2004_Am.J.Hum.Genet_75_112
Author(s) : Feng Y , Niu T , Xing H , Xu X , Chen C , Peng S , Wang L , Laird N
Ref : American Journal of Human Genetics , 75 :112 , 2004
Abstract : Nicotine is the major addictive substance in cigarettes, and genes involved in sensing nicotine are logical candidates for vulnerability to nicotine addiction. We studied six single-nucleotide polymorphisms (SNPs) in the CHRNA4 gene and four SNPs in the CHRNB2 gene with respect to nicotine dependence in a collection of 901 subjects (815 siblings and 86 parents) from 222 nuclear families with multiple nicotine-addicted siblings. The subjects were assessed for addiction by both the Fagerstrom Test for Nicotine Dependence (FTND) and the Revised Tolerance Questionnaire (RTQ). Because only 5.8% of female offspring were smokers, only male subjects were included in the final analyses (621 men from 206 families). Univariate (single-marker) family-based association tests (FBATs) demonstrated that variant alleles at two SNPs, rs1044396 and rs1044397, in exon 5 of the CHRNA4 gene were significantly associated with a protective effect against nicotine addiction as either a dichotomized trait or a quantitative phenotype (i.e., age-adjusted FTND and RTQ scores), which was consistent with the results of the global haplotype FBAT. Furthermore, the haplotype-specific FBAT showed a common (22.5%) CHRNA4 haplotype, GCTATA, which was significantly associated with both a protective effect against nicotine addiction as a dichotomized trait (Z=-3.04, P<.005) and significant decreases of age-adjusted FTND (Z=-3.31, P<.005) or RTQ scores (Z=-2.73, P=.006). Our findings provide strong evidence suggesting a common CHRNA4 haplotype might be protective against vulnerability to nicotine addiction in men.
ESTHER : Feng_2004_Am.J.Hum.Genet_75_112
PubMedSearch : Feng_2004_Am.J.Hum.Genet_75_112
PubMedID: 15154117

Title : Crystallization and preliminary crystallographic analysis of acylamino-acid releasing enzyme from the hyperthermophilic archaeon Aeropyrum pernix - Wang_2002_Acta.Crystallogr.D.Biol.Crystallogr_58_1054
Author(s) : Wang G , Gao R , Ding Y , Yang H , Cao S , Feng Y , Rao Z
Ref : Acta Crystallographica D Biol Crystallogr , 58 :1054 , 2002
Abstract : Crystals of acylamino-acid releasing enzyme from the hyperthermophilic archaeon Aeropyrum pernix strain K1 have been grown at 291 K using ammonium phosphate as a precipitant. The diffraction pattern of the crystal extends to 2.4 A resolution at 100 K using Cu Kalpha radiation. The crystal belongs to space group P1, with unit-cell parameters a = 107.5, b = 109.9, c = 119.4 A, alpha = 108.1, beta = 109.8, gamma = 91.9 degrees. The presence of eight molecules per asymmetric unit gives a crystal volume per protein mass (V(M)) of 2.4 A(3) Da(-1) and a solvent content of 48% by volume. A full set of X-ray diffraction data was collected to 2.9 A from the native crystal.
ESTHER : Wang_2002_Acta.Crystallogr.D.Biol.Crystallogr_58_1054
PubMedSearch : Wang_2002_Acta.Crystallogr.D.Biol.Crystallogr_58_1054
PubMedID: 12037315
Gene_locus related to this paper: aerpe-APE1547

Title : [Evaluation of screening methods for cholinesterase variants from daily laboratory data] - Feng_1999_Rinsho.Byori_47_749
Author(s) : Feng Y , Dey DC , Kondo A , Yonekawa O , Kanno T
Ref : Rinsho Byori , 47 :749 , 1999
Abstract : The genetic variants of the cholinesterase (ChE) are frequently misdiagnosed as a liver dysfunction. We compared three extraction methods for screening of ChE abnormalities. Employing these three methods, total 31 cases were found to be genetic abnormalities from 2985 patients of Hamamatsu University Hospital. We picked up 11 of candidates with low enzyme activities less than 100U/l as group 1 using the first method and effectively detected 9 cases (82%) with genetic abnormalities. The second extraction method was based on the ratio between Albumin (Alb) and ChE and subsequently, 48 of high risk patients were picked up as group 2 and 28 cases (58%) showed genetic abnormalities. Furthermore, all cases of group 1 were contained in the second group. The third method was based on the discrimination function from Alb and total cholesterol (TC) as group 3 and 32 cases were picked up. Fourteen cases (44%) out of them showed the genetic abnormalities using this method, and surprisingly, 13 cases (93%) of them were estimated to be K-variant. Although the three methods showed the different characteristics to extract genetic abnormalities of ChE, the second extraction method could pick up the largest population with genetic abnormalities. Further phenotypic extraction methods should be compared to understand the relationship between phenotype and genotype.
ESTHER : Feng_1999_Rinsho.Byori_47_749
PubMedSearch : Feng_1999_Rinsho.Byori_47_749
PubMedID: 10511807

Title : [Environmental pollution, human exposure and its health effect of sodium pentachlorophenate in schistosomiasis prevalent area] - Zheng_1997_Wei.Sheng.Yan.Jiu_26_24
Author(s) : Zheng X , Feng Y , Jiang X , Lu H , Wan Y , Fang YQ , Li YP , Huang XY , Li ZL , Fu WZ , Wang XH , Lin YZ , Zhang Z
Ref : Wei Sheng Yan Jiu , 26 :24 , 1997
Abstract : Sodium pentachlorophenate (Na-PCP) has been used in China for years as an molluscacide to kill oncomelania, which is an intermediate host of Schistosome. To evaluate the effects of its long-term successive usage on environment, human exposure and health, studies were carried out in Sichuan, Jiangxi, Jiangsu and Fujian provinces, with a time gap of more than one month between sample collection and last spray of Na-PCP. Results indicated that PCP contents in surface water, soil, sediment, animals and plants were significantly higher in studied areas than in control areas. The daily intake and the content in urine of PCP were also sigificantify higher in studied areas. But, there was no difference on physical and biochemical examinations except that a 22%-28% decrease of blood cholinesterase activity was found in studied areas. The health effect of impurities in Na-PCP, dioxins and furans, was assessed and discussed.
ESTHER : Zheng_1997_Wei.Sheng.Yan.Jiu_26_24
PubMedSearch : Zheng_1997_Wei.Sheng.Yan.Jiu_26_24
PubMedID: 15747456

Title : Changes in the endplate accumulation of acetylcholinesterase during synapse elimination in the mouse - Feng_1994_Brain.Res.Dev.Brain.Research_79_151
Author(s) : Feng Y , Carlson CG
Ref : Brain Research Developmental Brain Research , 79 :151 , 1994
Abstract : Focal accumulations of acetylcholinesterase (AChE; EC 3.1.1.7), cholinesterase (ChE, EC 3.1.1.8) and total cholinesterase (TChE; AChE+ChE) were examined in developing mouse diaphragm by using a modified Karnovsky/Roots staining method. The lengths of TChE and AChE reaction product accumulations reached significant peaks on postnatal day (PD) 1 (P < 0.05), decreased to a minimum on PD 9 and then increased in proportion to muscle fiber diameter (PD 9 to adult). The normalized area of accumulation (area of accumulation/fiber diameter) for AChE and TChE also decreased by 19% (P < 0.05) between PD 3 and PD 7. In contrast, ChE focal accumulation did not decrease during the period of synapse elimination, but rather increased in proportion to the postnatal growth of the muscle fiber. These results suggest that AChE is more sensitive to neurotrophic influences than ChE; particularly during late embryonic and early postnatal periods of synapse elimination.
ESTHER : Feng_1994_Brain.Res.Dev.Brain.Research_79_151
PubMedSearch : Feng_1994_Brain.Res.Dev.Brain.Research_79_151
PubMedID: 7955314