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检索条件"任意字段=中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议"

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Structure of the NS5 methyltransferase from Zika virus and implications in inhibitor design

Structure of the NS5 methyltransferase from Zika virus and i...

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中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议

作者： Caiying Zhang Tingting Feng Jinbo Cheng Yajuan Li Xueying Yin Weihong Zeng Xiangyu Jin Yuelong Li Feng Guo Tengchuan Jin Laboratory of Structural Immunology University of Science and Technology of China School of Medicine Stanford University

Recent outbreak of flavivirus Zika virus(ZIKV) in America has urged the basic as well as translational studies of this important human *** nonstructural protein 5(NS5) of the flavivirus has an N terminal methyltransferase(MTase) domain that plays critical roles in viral RNA genome *** null mutant of NS5 MTase is lethal for ***,NS5 is a potential drug target for the treatment of Zika virus *** this study,we determined crystal structures of the ZIKV MTase in complex with GTP and RNA cap analogue 7 *** analyses revealed highly conserved GTP/cap-binding pocket and S-adenosylmethionine(SAM)-binding *** conformations of the second base of the cap were identified,which suggests the flexibility of RNA *** addition,the ligand binding pockets identified a continuous region of hotspots suitable for drug *** calculation shows that the Dengue virus inhibitor compound 10 may bind to the ZIKV MTase.

关键词： Flavivirus family virus Zika virus Methyltransferase RNA cap Antiviral inhibitor design

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Effect of Mg-deficiency on Neurological Disorders

Effect of Mg-deficiency on Neurological Disorders

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中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议

作者： Xiangcui Chen Wenwen Xue Qinglu Wang Key Laboratory of Biomedical Engineering & Technology Qilu Medical University

Magnesium(Mg) is the second abundant intracellular cation and the fourth abundant elements in the *** it plays a complex function in our body,Mg,which accounts for only 0.05 % of body weight and regards as the least macro element of human body,is considered as an important element for human *** being an activator of many enzymes,Mg is involved in the metabolism and neurotransmission of the three major nutrients in the ***,Mg displays two different characteristics of deficiency in nervous system: acute Mg deficiency and chronic Mg *** Mg deficiency leads to metabolic encephalopathy and the changing of neuromuscular excitability,for instance,deprementia and *** chronic Mg deficiency can display in a symptom as *** we have already known the potential role of Mg in neurological disease for decades,it is still difficult to pin down the clinical arena of *** research demonstrates that deficiency of Mg leads to neurological disorders ranging from apathy to *** it has been reported that Mg has an effect on synaptic plasticity of ***,there are also some studies suggesting a neuroprotective action for Mg in the synaptic *** an in vitro study with mouse neurons,Mg can inhibit the release of glutamate and activate the N-methyl-D-aspartate(NMDA)-*** to Ca2+,it can also act as a cell signaling molecule and play multiple important roles in the functions of nerve,muscle and immune system.

关键词： Magnesium Neurological disorders Magnesium deficiency Cerebral vasospasm Alzheimer's disease Stroke Migraine

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Rational Design of Protein Fibrils Using α-helices as Building Blocks

Rational Design of Protein Fibrils Using α-helices as Build...

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中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议

作者： Xiangyu Sun Huabin Zhou Luhua Lai College of Chemistry and Molecular Engineering Peking University Peking-Tsinghua Center for Life Sciences at College of Chemistry and Molecular Engineering Peking University

Amyloid fibrils play important roles in most neurodegenerative diseases like Parkinson's and Alzheimer's *** the aggregation process and sequence/structure determinants of amyloid fibrils can help understand the molecular mechanisms of their *** all known protein fibrils are formed by proteins with or that transform into β-sheet *** cases of fibrils constructed by α-helices have been ***,Staphylococcus aureus PSMα3 was found to form amyloid-like fibrils with a cross-α *** discovery suggests that α-helical proteins also have the potential to aggregate into fibrils and display important biological *** we show a de novo designed 18-residue amphiphilic α-helical peptide can aggregate into amyloid-like fibrils as observed in electron *** dichroism spectroscopy gave typical α-helical features both before and after *** dynamic simulations with all-atom or coarse-grained models indicate that the aggregates of this peptide are stable in *** the lengths of the fibrils differ,their widths were all about 20 *** demonstrated that amyloid-like fibrils can be rationally designed using amphiphilic helices as building blocks,which can be helpful to understand the structures of protein fibrils from a new perspective as well as to design new protein aggregates with biological functions.

关键词： Protein design Amyloid-like fibrils MD simulations

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Accelerating the throughput of affinity mass spectrometry-based ligand screening towards G-protein coupled receptors

Accelerating the throughput of affinity mass spectrometry-ba...

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中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议

作者： Yan Lu Shanshan Qin Wenqing Shui iHuman Institute ShanghaiTech University School of Life Science and Technology ShanghaiTech University

As an important transmembrane signaling modulator,G protein-coupled receptors(GPCRs) account for more than 30% of the marketed *** investigate ligand specificity to GPCRs,protein-ligand interaction can be analyzed by various technologies,such as SPR,NMR,ITC,*** recent years,affinity mass spectrometry(MS)-based platforms have gained increasing success in drug discovery mostly towards soluble protein ***,transmembrane proteins,especially GPCRs,remain challenging targets for affinity MS *** have previously established an efficient workflow for ligand screening towards GPCRs embedded in cell *** this study,we present another approach adapted to ligand screening towards purified receptor *** throughput of our GPCR ligand screening platform has been significantly accelerated by pooling tens of thousands of compounds in one ***-affinity ligands were repeatedly identified when we compared the hits from screening 2 K compounds up to 20 K compounds in one *** new antagonists for adenosine 2 A receptor have been discovered using our affinity MS ligand screens combined with cell activity assays,which demonstrates the high efficiency and reduced cost of our integrated platform for discovery of GPCR modulators.

关键词： GPCR ligand screening affinity MS adenosine 2A receptor

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Ursolic acid inhibits IL-1β-induced release of IL-6 and IL-8 via suppression of AKT, ERK and NF-kappa B pathways in SW982 human synovial cells

Ursolic acid inhibits IL-1β-induced release of IL-6 and IL-...

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中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议

作者： Hao-heng Yu Chuan He Bin-Feng Cheng College of Life Science and Technology Xinxiang Medical University

Ursolic acid(Ursolic acid,UA),a pentacyclic triterpenoid compound present in a wide variety of plant foods,is reported to have anti-inflammatory,anti-tumor,anti-oxidant and anti-diabetes and other biological ***,the effects and mechanisms of UA in the interleukin(IL)-1β-stimulated human synovial sarcoma cell line SW982,a useful tool to investigate expression of inflammatory mediators involved in rheumatoid arthritis,have not been elucidated to *** this study,SW982 cells were pretreated with UA at various concentrations(1 and 5 μM) followed by IL-1β(10 ng/mL) *** found that UA significantly inhibited protein and gene expression levels of IL-6 and *** inhibited phosphorylation of extracellular signal-regulated kinase(ERK),p65 and *** also suppressed the degradation of IκBα and blocked p65 translocation into *** results demonstrated that the expression levels of inflammatory mediators in SW982 cells induced by IL-1β were decreased by UA via suppression of AKT,ERK and NF-kappa B pathways.

关键词： Ursolic acid SW982 cells Inflammatory factors IL-1 beta Signal pathway

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Decomposition of D-Ribose Producing Formaldehyde

Decomposition of D-Ribose Producing Formaldehyde

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中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议

作者： Lexiang Yu Yujing Wang Yao Chen Yan Wei Rongqiao He State Key Laboratory of Brain and Cognitive Science Institute of BiophysicsUniversity of Chinese Academy of Sciences Southwest Medical University Alzheimer's Disease Center Beijing Institute for Brain DisordersCapital Medical University

Although D-ribose is reputedly a key "anti-aging nutrient" and provided as a supplement to elderly people to improve their health,no laboratories have reported that D-ribose is involved in the production of formaldehyde(FA) under the physiological pH *** is toxic and has been implicated in the pathologies of various diseases,such as neurodegenerative diseases and ***,to improve the safety of D-ribose supplementation,we show that formaldehyde can be produced from decomposition of D-ribose in solution.D-ribose first decomposed into glyceraldehyde(GA),followed by production of formaldehyde under neutral and alkaline *** experiments showed that formaldehyde was produced in the presence of D-ribose in a lysine *** formaldehyde is produced in the presence of norleucine(containing an α-amino group) compared with 6-aminocaproic acid(containing an ε-amino group),which indicates that the α-amino group of amino acids plays an active role in the decomposition of *** with glycine further confirmed this *** work suggests the concentration of formaldehyde produced during administration of D-ribose should be carefully monitored in the elderly who are receiving D-ribose as an anti-aging supplement.

关键词： D-ribose formaldehyde anti-aging nutrient glyceraldehyde

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Dkk3 dependent transcriptional regulation controls age related skeletal muscle atrophy

Dkk3 dependent transcriptional regulation controls age relat...

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中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议

作者： Jie Yin Lele Yang Yangli Xie Hongbin Ji Lin Chen Ping Hu State Key Laboratory of Cell Biology CAS Center for Excellence in Molecular Cell SciencesShanghai Institute of Biochemistry and Cell BiologyShanghai Institutes for Biological SciencesChinese Academy of Sciences CAS Center for Excellence in Molecular Cell Science Shanghai Institute of Biochemistry and Cell BiologyChinese Academy of SciencesUniversity of Chinese Academy of Sciences Department of Rehabilitation Medicine Center of Bone Metabolism and RepairState Key Laboratory of TraumaBurns and Combined InjuryTrauma CenterResearch Institute of SurgeryDaping HospitalThe Third Military Medical University State Key Laboratory of Molecular Biology CAS Center for Excellence in Molecular Cell SciencesShanghai Institutes for Biological SciencesChinese Academy of Sciences

Age-related muscle atrophy (sarcopenia) is the leading cause for disability in aged population, but the underlying molecular mechanisms are poorly understood. Here we identify a novel role for the secreted glycoprotein Dickkopf 3 (Dkk3) in sarcopenia.. Forced expression of Dkk3 in muscles in young mice leads to muscle atrophy. Conversely, reducing its expressionin old muscles restores both muscle size and

关键词： Dkk3 dependent transcriptional regulation controls age related skeletal muscle atrophy

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SUMOylation of IQGAP1 promotes the development of colorectal cancer

SUMOylation of IQGAP1 promotes the development of colorectal...

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中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议

作者： Yanfang Yang Ziwei Liang Yu He Xixi Wang Shufang Liang State Key Laboratory of Biotherapy and Cancer Center West China HospitalSichuan Universityand Collaborative Innovation Center for Biotherapy

IQGAP1 is a conserved multifunctional protein implicated in *** aberrant expression of IQGAP1 widely exists in many cancers,but the SUMOylation modification of IQGAP1 in carcinogenesis is unknown by *** we first time explore biological functions of IQGAP1 SUMOylation in promoting colorectal cancer progression in vitro and in *** expression of IQGAP1 and its SUMOylation level are both increased in human colorectal carcinoma(CRC) cells and ***1 is mainly SUMOylated by SUMO1 at the K1445 residue,which could stabilize IQGAP1 by reducing protein ***1 SUMOylation improves CRC cell growth,cell migration and tumorigenesis in vivo through activating the phosphorylation of ERK,MEK and *** the SUMOylation site mutation at K1445 of IQGAP1 greatly reduces CRC cell proliferation,migration ability and tumor growth of CRC-xenograft mice by suppressing phosphorylation of ERK,MEK and *** findings discover the IQGAP1 SUMOylation is a novel regulatory mechanism to enhance tumorigenesis and development of CRC in vitro and in vivo.

关键词： IQGAP1 colorectal carcinoma SUMOylation SUMO1

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Biocatalytic Preparation of Chiral Sulfoxides by recombinant Methionine Sulfoxide Reductase A

Biocatalytic Preparation of Chiral Sulfoxides by recombinant...

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中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议

作者： Liaotian Peng Yuanmei Wen Zhimei Yuan Yang Zhou Jiawei Yang Department of Biochemistry Zunyi Medical University

Chiral sulfoxides are valuable organosulfur compounds and have been widely used as important intermediates in asymmetric synthesis and as bioactive ingredients in pharmaceutical *** biocatalysis is a new approach for green synthesis of chiral ***,it is difficult to obtain enzymes with high catalytic efficiency and high substrate *** this study,a methionine sulfoxide reductase A gene was cloned from a Pseudomonas monteilii strain(named pm MsrA) and recombinant expressed in *** results show that this enzyme can effectively accomplish the preparation of(R)-sulfoxides with approximately 50% yield and 94–99% enantiomeric excess through asymmetric reductive resolution of racemic *** the establishment of the enzyme regeneration system,the(R)-sulfoxides were obtained with high enantioselectivity under the substrate concentration up to 200 mm(approximately 32 g/L),representing a quite high substrate concentration in biocatalytic preparation of chiral ***,this enzyme showed fairly good activity and enantioselectivity towards a series of ortho-and para-substituted phenyl methyl *** high initial substrate concentration,catalytic rate,and operability,as well as wide substrate scope of our system implies a potential future for industrial *** addition,the discovery and application of the pm MsrA strongly supports that asymmetric reductive resolution of rac-sulfoxides could be an alternative strategy for green synthesis of optically pure sulfoxides.

关键词： Methionine sulfoxide reductase A recombinant enzyme chiral sulfoxides biocatalysis

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DptP protein is required for exporting of daptomycin in Streptomyces roseosporus

DptP protein is required for exporting of daptomycin in Stre...

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中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议

作者： Dan Zhang Yang Ye Yu He Shufang Liang State Key Laboratory of Biotherapy and Cancer Center West China HospitalSichuan University/National Collaborative Innovation Center for Biotherapy

Daptomycin(DAP),a cyclic lipopeptide produced by Streptomyces roseosporus(***),is a novel antibiotic against Gram-positive *** dptP gene locates upstream of the DAP gene cluster dpt,and its encoding protein shares a significant sequence similarity with Ded A family membrane proteins,which is required for growth or drug *** function of dptP gene has not been clarified in *** study aims to decipher the biological roles of dptP on expression levels of dpt members,strain growth and DAP export through gain-and loss-of-function experiments and microbiological proteomic *** deletion of dptP gene by a CRISPR-Cas9 system increases transcription levels of biosynthetic genes,including dptA,dptBC,dptE,dptF,but decreases the transcription levels of the transporter-related dptM and ***,dptP knockout significantly inhibits growth tolerance of Streptomyces species to 500 ug/ml DAP *** overexpression of dptP induces the reverse biological effects in ***,proteomic analysis for the dptP-deleted strain confirms that dptP-regulated proteins mainly include transporters,carbon metabolism,biosynthesis of amino *** conclusion,dpt P gene enhances the transcription of transporter-related genes,and its encoding protein contributes to DAP export as a transporter.

关键词： Daptomycin dptP gene gene cluster proteome Streptomyces roseosporus

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