pH-dependent conformational flexibility of the SARS-CoV main proteinase (M-pro) dimer: Molecular dynamics simulations and multiple X-ray structure analyses
文献类型：期刊论文
| 作者 | Tan, JZ; Verschueren, KHG; Anand, K; Shen, JH ; Yang, MJ; Xu, YC; Rao, ZH; Bigalke, J; Heisen, B; Mesters, JR
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| 刊名 | JOURNAL OF MOLECULAR BIOLOGY
 |
| 出版日期 | 2005-11-18 |
| 卷号 | 354期号:1页码:25-40 |
| 关键词 | SARS-CoV M-pro molecular dynamics simulation new crystal forms multiple X-ray structures conformational flexibility |
| ISSN号 | 0022-2836 |
| DOI | 10.1016/j.jmb.2005.09.012 |
| 文献子类 | Article |
| 英文摘要 | The SARS coronavirus main proteinase (M-pro) is a key enzyme in the processing of the viral polyproteins and thus an attractive target for the discovery of drugs directed against SARS. The enzyme has been shown by X-ray crystallography to undergo significant pH-dependent conformational changes. Here, we assess the conformational flexibility of the Mpro by analysis of multiple crystal structures (including two new crystal forms) and by molecular dynamics (MD) calculations. The MD simulations take into account the different protonation states of two histidine residues in the substrate-binding site and explain the pH-activity profile of the enzyme. The low enzymatic activity of the Mpro monomer and the need for dimerization are also discussed. (c) 2005 Elsevier Ltd. All rights reserved. |
| WOS关键词 | ACUTE RESPIRATORY SYNDROME ; CORONAVIRUS 3C-LIKE PROTEINASE ; ELECTRON-DENSITY ; DESIGN ; INHIBITORS ; PROTEASE ; BIOSYNTHESIS ; PURIFICATION ; DIMERIZATION ; MECHANISMS |
| WOS研究方向 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000233310800003 |
| 出版者 | ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/273772]  |
| 专题 | 药物发现与设计中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Jiang, HL |
| 作者单位 | 1.Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing 100101, Peoples R China 2.Med Univ Lubeck, Inst Biochem, Ctr Struct & Cell Biol Med, D-23538 Lubeck, Germany 3.Tsing Hua Univ, Grp Struct Biol, Tsinghua IBP Joint REs, Beijing 100084, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Biol Sci, Grad Sch,Ctr Drug Discovery & Design, Shanghai Inst Mat Med,State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Tan, JZ,Verschueren, KHG,Anand, K,et al. pH-dependent conformational flexibility of the SARS-CoV main proteinase (M-pro) dimer: Molecular dynamics simulations and multiple X-ray structure analyses[J]. JOURNAL OF MOLECULAR BIOLOGY,2005,354(1):25-40. |
| APA | Tan, JZ.,Verschueren, KHG.,Anand, K.,Shen, JH.,Yang, MJ.,...&Hilgenfeld, R.(2005).pH-dependent conformational flexibility of the SARS-CoV main proteinase (M-pro) dimer: Molecular dynamics simulations and multiple X-ray structure analyses.JOURNAL OF MOLECULAR BIOLOGY,354(1),25-40. |
| MLA | Tan, JZ,et al."pH-dependent conformational flexibility of the SARS-CoV main proteinase (M-pro) dimer: Molecular dynamics simulations and multiple X-ray structure analyses".JOURNAL OF MOLECULAR BIOLOGY 354.1(2005):25-40. |
入库方式： OAI收割
来源：上海药物研究所
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