Ni Y

References (13)

Title : Structural and mechanistic insights into enantioselectivity toward near-symmetric esters of a novel carboxylesterase RoCE - Dou_2022_Catal.Sci.Technol_12_7448
Author(s) : Dou Z , Jia P , Chen X , Wu Z , Xu G , Ni Y
Ref : Catal Sci Technol , 12 :7448 , 2022
Abstract : A novel carboxylesterase designated as RoCE was identified from Rhodococcus opacus with high activity and enantioselectivity toward asymmetric esters such as ethyl 2,2-dimethylcyclopropane-1-carboxylate (DMCPE). Moreover, RoCE could catalyze the enantioselective resolution of near-symmetric oxyheterocyclic esters such as ethyl tetrahydro-2H-pyran-2-carboxylate (THPCE), which are generally regarded as 'hard-to-be-discriminated' by chemical and biological catalysts. The crystal structure of RoCE was resolved at a resolution of 1.78 A. Theozyme calculation, MD simulations and pre-reaction state analysis were performed to clarify the molecular basis for the enantioselectivity toward oxyheterocyclic carboxylic acid esters with a nearly symmetric structure. F166 plays an important role in manipulating the enantioselective recognition of (S)- and (R)-DMCPE through steric effect. The intrinsic symmetric structure of (S)- and (R)-THPCE is mainly responsible for the relatively lower enantioselectivity than DMCPE. By introducing hydrogen bond interactions, a mutant M144T was successfully obtained with an E value of 2.44-fold that of WT. MD simulations further prove the increased enantioselectivity of M144T in terms of pre-reaction state and binding free energy. This study provides a novel carboxylesterase and important molecular insights into the enantioselectivity of carboxylesterase toward heterocyclic carboxylic acid esters with a nearly symmetric structure, which will facilitate further engineering of the enantioselectivity of carboxylesterase.
ESTHER : Dou_2022_Catal.Sci.Technol_12_7448
PubMedSearch : Dou_2022_Catal.Sci.Technol_12_7448
PubMedID:
Gene_locus related to this paper: rhoop-RoCE

Title : Neurotoxins Acting at Synaptic Sites: A Brief Review on Mechanisms and Clinical Applications - Zhou_2022_Toxins.(Basel)_15_
Author(s) : Zhou K , Luo W , Liu T , Ni Y , Qin Z
Ref : Toxins (Basel) , 15 : , 2022
Abstract : Neurotoxins generally inhibit or promote the release of neurotransmitters or bind to receptors that are located in the pre- or post-synaptic membranes, thereby affecting physiological functions of synapses and affecting biological processes. With more and more research on the toxins of various origins, many neurotoxins are now widely used in clinical treatment and have demonstrated good therapeutic outcomes. This review summarizes the structural properties and potential pharmacological effects of neurotoxins acting on different components of the synapse, as well as their important clinical applications, thus could be a useful reference for researchers and clinicians in the study of neurotoxins.
ESTHER : Zhou_2022_Toxins.(Basel)_15_
PubMedSearch : Zhou_2022_Toxins.(Basel)_15_
PubMedID: 36668838

Title : Kinetic Resolution of Nearly Symmetric 3-Cyclohexene-1-carboxylate Esters Using a Bacterial Carboxylesterase Identified by Genome Mining - Dou_2021_Org.Lett__
Author(s) : Dou Z , Chen X , Niwayama S , Xu G , Ni Y
Ref : Org Lett , : , 2021
Abstract : A new bacterial carboxylesterase (CarEst3) was identified by genome mining and found to efficiently hydrolyze racemic methyl 3-cyclohexene-1-carboxylate (rac-CHCM) with a nearly symmetric structure for the synthesis of (S)-CHCM. CarEst3 displayed a high substrate tolerance and a stable catalytic performance. The enantioselective hydrolysis of 4.0 M (560 g.L(-1)) rac-CHCM was accomplished, yielding (S)-CHCM with a >99% ee, a substrate to catalyst ratio of 1400 g.g(-1), and a space-time yield of 538 g.L(-1).d(-1).
ESTHER : Dou_2021_Org.Lett__
PubMedSearch : Dou_2021_Org.Lett__
PubMedID: 33797267
Gene_locus related to this paper: 9gamm-a0a3b7mcl8

Title : A novel carboxylesterase from Acinetobacter sp. JNU9335 for efficient biosynthesis of Edoxaban precursor with high substrate to catalyst ratio - Dou_2020_Bioresour.Technol_317_123984
Author(s) : Dou Z , Xu G , Ni Y
Ref : Bioresour Technol , 317 :123984 , 2020
Abstract : A novel carboxylesterase AcEst1 was identified from Acinetobacter sp. JNU9335 with high efficiency in the biosynthesis of chiral precursor of Edoxaban through kinetic resolution of methyl 3-cyclohexene-1-carboxylate (CHCM). Sequence analysis revealed AcEst1 belongs to family IV of esterolytic enzymes and exhibits <40% identities with known carboxylesterases. The optimum pH and temperature of recombinant AcEst1 are 8.0 and 40 degC. Substrate spectrum analysis indicated that AcEst1 prefers substrates with short acyl and alcohol groups. AcEst1 was highly active in the hydrolysis of CHCM with k(cat) of 1153 s(-1) and displayed high substrate tolerance. As much as 2.0 M (280 g.L(-1)) CHCM could be enantioselectively hydrolyzed into (S)-CHCM by merely 0.08 g.L(-1)AcEst1 with ee(s) of >99% (S) and substrate to catalyst ratio (S/C) of 3500 g.g(-1). These results indicate that the novel AcEst1 is a promising biocatalyst in the synthesis of chiral carboxylic acids.
ESTHER : Dou_2020_Bioresour.Technol_317_123984
PubMedSearch : Dou_2020_Bioresour.Technol_317_123984
PubMedID: 32827974
Gene_locus related to this paper: 9gamm-a0a7h9sp49

Title : Low Plasma Cholinesterase Activity is Associated With Postoperative Delirium After Noncardiac Surgery in Elderly Patients: AProspective Observational Study - Zhao_2019_Psychosomatics_60_190
Author(s) : Zhao B , Ni Y , Tian X
Ref : Psychosomatics , 60 :190 , 2019
Abstract : BACKGROUND: Postoperative delirium (POD) commonly occurs in elderly patients after noncardiac surgery, resulting in increased morbidity and greater risk of death. However, its pathophysiology is currently unknown. Cholinergic dysfunction has been implicated in delirium pathophysiology, and low plasma cholinesterase activity has been reported as a risk marker of POD. OBJECTIVE: Therefore, the aim of this study was to investigate the link between plasma cholinesterase activity and POD in elderly Han Chinese patients after noncardiac surgery. METHOD: From January 2014 to January 2016, a cohort of 206 patients aged >/= 60years who underwent noncardiac surgery and were transferred to the surgical intensive care unit were enrolled. POD was assessed using the Confusion Assessment Method for Intensive Care Unit. Clinical data including sex, age, general comorbidities, alcohol consumption, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and type of surgery were recorded. Blood was drawn postoperatively to measure cholinesterase activity. Using multiple logistic regression analyses, the associations between cholinesterase activity and POD were examined, adjusting for potential confounding variables. RESULTS: Delirium incidence was 22.3%. POD was associated with cholinesterase activity, age, and APACHE II score. In multiple logistic regression analyses, lower acetylcholinesterase and butyrylcholinesterase activity were independent risk factors for POD. CONCLUSION: Plasma cholinesterase activity may be a candidate biomarker for POD after noncardiac surgery in the elderly Chinese Han population.
ESTHER : Zhao_2019_Psychosomatics_60_190
PubMedSearch : Zhao_2019_Psychosomatics_60_190
PubMedID: 30093245

Title : A novel variant associated with HDL-C levels by modifying DAGLB expression levels: An annotation-based genome-wide association study - Zhou_2018_Eur.J.Hum.Genet_26_838
Author(s) : Zhou D , Zhang D , Sun X , Li Z , Ni Y , Shan Z , Li H , Liu C , Zhang S , Liu Y , Zheng R , Pan F , Zhu Y , Shi Y , Lai M
Ref : Eur J Hum Genet , 26 :838 , 2018
Abstract : Although numbers of genome-wide association studies (GWAS) have been performed for serum lipid levels, limited heritability has been explained. Studies showed that combining data from GWAS and expression quantitative trait loci (eQTLs) signals can both enhance the discovery of trait-associated SNPs and gain a better understanding of the mechanism. We performed an annotation-based, multistage genome-wide screening for serum-lipid-level-associated loci in totally 6863 Han Chinese. A serum high-density lipoprotein cholesterol (HDL-C) associated variant rs1880118 (hg19 chr7:g. 6435220G>C) was replicated (Pcombined = 1.4E-10). rs1880118 was associated with DAGLB (diacylglycerol lipase, beta) expression levels in subcutaneous adipose tissue (P = 5.9E-42) and explained 47.7% of the expression variance. After the replication, an active segment covering variants tagged by rs1880118 near 5' of DAGLB was annotated using histone modification and transcription factor binding signals. The luciferase report assay revealed that the segment containing the minor alleles showed increased transcriptional activity compared with segment contains the major alleles, which was consistent with the eQTL analyses. The expression-trait association tests indicated the association between the DAGLB and serum HDL-C levels using gene-based approaches called "TWAS" (P = 3.0E-8), "SMR" (P = 1.1E-4), and "Sherlock" (P = 1.6E-6). To summarize, we identified a novel HDL-C-associated variant which explained nearly half of the expression variance of DAGLB. Integrated analyses established a genotype-gene-phenotype three-way association and expanded our knowledge of DAGLB in lipid metabolism.
ESTHER : Zhou_2018_Eur.J.Hum.Genet_26_838
PubMedSearch : Zhou_2018_Eur.J.Hum.Genet_26_838
PubMedID: 29476167

Title : Inhibition effect of graphene oxide on the catalytic activity of acetylcholinesterase enzyme - Wang_2015_Luminescence_30_940
Author(s) : Wang Y , Gu Y , Ni Y , Kokot S
Ref : Luminescence , 30 :940 , 2015
Abstract : Variations in the enzyme activity of acetylcholinesterase (AChE) in the presence of the nano-material, graphene oxide (GO), were investigated with the use of molecular spectroscopy UV-visible and fluorescence methods. From these studies, important kinetic parameters of the enzyme were extracted; these were the maximum reaction rate, Vm , and the Michaelis constant, Km . A comparison of these parameters indicated that GO inhibited the catalytic activity of the AChE because of the presence of the AChE-GO complex. The formation of this complex was confirmed with the use of fluorescence data, which was resolved with the use of the MCR-ALS chemometrics method. Furthermore, it was found that the resonance light-scattering (RLS) intensity of AChE changed in the presence of GO. On this basis, it was demonstrated that the relationship between AChE and GO was linear and such models were used for quantitative analyses of GO. Copyright (c) 2015 John Wiley & Sons, Ltd.
ESTHER : Wang_2015_Luminescence_30_940
PubMedSearch : Wang_2015_Luminescence_30_940
PubMedID: 25620714

Title : Increased Catalyst Productivity in alpha-Hydroxy Acids Resolution by Esterase Mutation and Substrate Modification - Ma_2014_ACS.Catal_4_1026
Author(s) : Ma BD , Kong XD , Yu HL , Zhang ZJ , Dou S , Xu YP , Ni Y , Xu JH
Ref : ACS Catal , 4 :1026 , 2014
Abstract : Optically pure alpha-hydroxy acids and their derivatives are versatile chiral building blocks in the pharmaceutical industry. In this study, the potential of a recombinant Pseudomonas putida esterase (rPPE01) for the enzymatic resolution of -acetoxy acids was significantly improved by combinatorial engineering of both the biocatalyst and substrate. Semirational design based on homologous modeling and molecular docking provided a single-point variant, W187H, whose kcat/KM for sodium 2-acetoxy-2-(2'-chlorophenyl)acetate (Ac-CPA-Na) was increased 100-fold, from 0.0611 to 6.20 mM-1 s-1, while retaining its excellent enantioselectivity and broad substrate spectrum. Biocatalyst deactivation under the operating conditions was decreased by using the potassium salt of Ac-CPA instead of Ac-CPA-Na. With 0.5 g L-1 of lyophilized cells containing rPPE01-W187H, 500 mM (R,S)-Ac-CPA-K was selectively deacylated with 49.9% conversion within 15 h, giving satisfactory enantiomeric excesses (ee) for both the S product (>99% ee) and the remaining R substrate (98.7% ee). Consequently, the amount of (S)-2-hydroxy-2-(2'-chlorophenyl)acetate prepared per unit weight of lyophilized cells was improved by a factor of 18.9 compared with the original productivity of the wild-type esterase. Further enzymatic resolution of other important hydroxy acids at the 100 mL scale demonstrated that the rPPE01-W187H-based bioprocess is versatile and practical for the large-scale preparation of chiral -hydroxy acids
ESTHER : Ma_2014_ACS.Catal_4_1026
PubMedSearch : Ma_2014_ACS.Catal_4_1026
PubMedID:
Gene_locus related to this paper: 9psed-l7pyq2

Title : Highly efficient biosynthesis of sucrose-6-acetate with cross-linked aggregates of Lipozyme TL 100 L - Yang_2012_J.Biotechnol_161_27
Author(s) : Yang X , Zheng P , Ni Y , Sun Z
Ref : J Biotechnol , 161 :27 , 2012
Abstract : As a short chain monoester, sucrose-6-acetate (S-6-a) is a key intermediate in the preparation of an eminent sweetener (sucralose). To replace the traditional multi-step chemical route for sucralose biosynthesis, enzymatic synthesis of S-6-a was investigated, using cross-linked enzyme aggregates (CLEAs) of Lipozyme TL 100 L. The optimal CLEA preparation conditions was obtained as follows: using 33.3% (v/v) PEG600 co-precipitated with additive of D-sorbierite, then cross-linking with 1.5% (v/v) glutaraldehyde at 0 degreeC for 4 h. As a result, the immobilized Lipozyme had high specific bioactivity (34.64 U/g) of transesterification in non-aqueous media. With these immobilized enzymes, the optimum transesterification conditions were investigated systematically, including CLEA loading, the mole ratio of vinyl acetate versus sucrose, temperature and reaction time, etc. The results showed that the highest concentration and yield of S-6-a was 49.8 g/L and 87.46%, respectively. Further experiments showed that the resulting CLEAs also had much higher operational stability than the commercial Lipozyme TLIM. The present work has paved a new path for the large-scale bioproduction of S-6-a with immobilized lipase in the future.
ESTHER : Yang_2012_J.Biotechnol_161_27
PubMedSearch : Yang_2012_J.Biotechnol_161_27
PubMedID: 22728393

Title : [Selective isolation and diversity of cold-adapted lipase-producing strains from permafrost soil at the terminus of a glacier in the Tianshan Mountains] - Xu_2011_Wei.Sheng.Wu.Xue.Bao_51_233
Author(s) : Xu Y , Wang D , Shi X , Zheng X , Zhou H , Liu Y , Ni Y
Ref : Wei Sheng Wu Xue Bao , 51 :233 , 2011
Abstract : OBJECTIVE: The diversity of culturable lipase-producing bacterial strains from permafrost soils at the terminus of a glacier in the Tianshan Mountains was investigated. Isolation and molecular phylogenetic analysis were performed to expand our knowledge on diversity of psychrotrophic and psychrophilic bacteria. In addition, efforts were made focusing on screening for cold active lipases. METHODS: Lipase-producing bacterial strains were detected on tween 80 and olive oil plates, respectively. Identity and genetic diversity of strains isolated were determined by spatial 16S rRNA gene sequences and rep-PCR fingerprint. The physiological tests were carried out to determine the phonotypic differences between strains showing high similarity of 16S rRNA gene sequences. RESULTS: Of the total 17 bacterial stains exhibiting cold-adapted lipase activity, we found that only 8 stains were able to hydrolyze olive oil. Based on 16S rRNA gene sequences, the lipase-producing bacterial isolates fell in five phylogenetic groups: subclasses (, ( and ( of Proteobacteria, Actinobacteria, and the Cytophaga-Flexibacter-Bacteroides (CFB) phylum. Nearly 59% of the isolates were affiliated with the genus Pseudomonas. CONCLUSION: The results enrich our knowledge on the psychrotrophic bacterial diversity and biogeographic distribution of cold active lipases-producing bacteria in cold environments.
ESTHER : Xu_2011_Wei.Sheng.Wu.Xue.Bao_51_233
PubMedSearch : Xu_2011_Wei.Sheng.Wu.Xue.Bao_51_233
PubMedID: 21574385

Title : Simultaneous enzymatic kinetic determination of pesticides, carbaryl and phoxim, with the aid of chemometrics - Ni_2007_Anal.Chim.Acta_588_131
Author(s) : Ni Y , Cao D , Kokot S
Ref : Anal Chim Acta , 588 :131 , 2007
Abstract : A sensitive and selective enzymatic kinetic method for the simultaneous determination of mixtures of carbaryl and phoxim pesticides was researched and developed. It was based on the inhibitory effect of the pesticides on acetylcholinesterase (AChE), and the use of 5,5'-dithiobis(2-nitrobenzoic) acid (DTNB) as a chromogenic reagent for the thiocholine iodide (TChI) released from the acetylthiocholine iodide (ATChI) substrate. The DTNB-thiocholine reaction was investigated by a spectrophotometric-kinetic approach. The complex rate equation for the formation of the chromogenic product, P, was solved under certain experimental conditions, which enabled the absorbance (A(P), at lambda(max)=412 nm) from the mixtures of the two pesticide inhibitors to be directly related to their concentrations provided the absorbance additivity was followed. The spectra were measured for mixtures of carbaryl and phoxim at different concentrations, and at t=904 s, T=35 degrees C, pH=7.5, c(ATChI)=0.14, and c(AChE)=0.10 mg mL(-1). The detection limits of the enzymatic kinetic spectrophotometric procedures for the determination of the carbaryl and phoxim were 4.7 and 0.59 microg L(-1), respectively. Calibration models for chemometrics methods, such as principal component regression (PCR), partial least squares (PLS) and radial basis function-artificial neural network (RBF-ANN) were constructed and verified with synthetic samples of the mixtures of the two pesticides. The best performing model was based on the RBF-ANN method yielding at approximately 10 ppb analyte concentrations, %RPE(T) (carbaryl=5.2; phoxim=6.5), %Recovery (approx.105%) and %RPE(T) (6.5). Various spiked town-water samples produced recoveries in the range of 98.8-103% for each pesticide.
ESTHER : Ni_2007_Anal.Chim.Acta_588_131
PubMedSearch : Ni_2007_Anal.Chim.Acta_588_131
PubMedID: 17386802

Title : Desensitization contributes to the synaptic response of gain-of-function mutants of the muscle nicotinic receptor - Elenes_2006_J.Gen.Physiol_128_615
Author(s) : Elenes S , Ni Y , Cymes GD , Grosman C
Ref : Journal of General Physiology , 128 :615 , 2006
Abstract : Although the muscle nicotinic receptor (AChR) desensitizes almost completely in the steady presence of high concentrations of acetylcholine (ACh), it is well established that AChRs do not accumulate in desensitized states under normal physiological conditions of neurotransmitter release and clearance. Quantitative considerations in the framework of plausible kinetic schemes, however, lead us to predict that mutations that speed up channel opening, slow down channel closure, and/or slow down the dissociation of neurotransmitter (i.e., gain-of-function mutations) increase the extent to which AChRs desensitize upon ACh removal. In this paper, we confirm this prediction by applying high-frequency trains of brief ( approximately 1 ms) ACh pulses to outside-out membrane patches expressing either lab-engineered or naturally occurring (disease-causing) gain-of-function mutants. Entry into desensitization was evident in our experiments as a frequency-dependent depression in the peak value of succesive macroscopic current responses, in a manner that is remarkably consistent with the theoretical expectation. We conclude that the comparatively small depression of the macroscopic currents observed upon repetitive stimulation of the wild-type AChR is due, not to desensitization being exceedingly slow but, rather, to the particular balance between gating, entry into desensitization, and ACh dissociation rate constants. Disruption of this fine balance by, for example, mutations can lead to enhanced desensitization even if the kinetics of entry into, and recovery from, desensitization themselves are not affected. It follows that accounting for the (usually overlooked) desensitization phenomenon is essential for the correct interpretation of mutagenesis-driven structure-function relationships and for the understanding of pathological synaptic transmission at the vertebrate neuromuscular junction.
ESTHER : Elenes_2006_J.Gen.Physiol_128_615
PubMedSearch : Elenes_2006_J.Gen.Physiol_128_615
PubMedID: 17074980

Title : Probing ion-channel pores one proton at a time - Cymes_2005_Nature_438_975
Author(s) : Cymes GD , Ni Y , Grosman C
Ref : Nature , 438 :975 , 2005
Abstract : Although membrane proteins often rely on ionizable residues for structure and function, their ionization states under physiological conditions largely elude experimental estimation. To gain insight into the effect of the local microenvironment on the proton affinity of ionizable residues, we have engineered individual lysines, histidines and arginines along the alpha-helical lining of the transmembrane pore of the nicotinic acetylcholine receptor. We can detect individual proton binding-unbinding reactions electrophysiologically at the level of a single proton on a single side chain as brief blocking-unblocking events of the passing cation current. Kinetic analysis of these fluctuations yields the position-dependent rates of proton transfer, from which the corresponding pK(a) values and shifts in pK(a) can be calculated. Here we present a self-consistent, residue-by-residue description of the microenvironment around the pore-lining transmembrane alpha-helices (M2) in the open-channel conformation, in terms of the excess free energy that is required to keep the engineered basic side chains protonated relative to bulk water. A comparison with closed-channel data leads us to propose that the rotation of M2, which is frequently invoked as a hallmark of the gating mechanism of Cys-loop receptors, is minimal, if any.
ESTHER : Cymes_2005_Nature_438_975
PubMedSearch : Cymes_2005_Nature_438_975
PubMedID: 16355215