Two adjacent mutations on the dimer interface of SARS coronavirus 3C-like protease cause different conformational changes in crystal structure
文献类型：期刊论文
| 作者 | Hu, Tiancen2; Zhang, Yu2; Li, Lianwei2; Wang, Kuifeng2; Chen, Shuai2; Chen, Jing2 ; Ding, Jianping1; Jiang, Hualiang2; Shen, Xu2
|
| 刊名 | VIROLOGY
 |
| 出版日期 | 2009-06-05 |
| 卷号 | 388期号:2页码:324-334 |
| 关键词 | SARS coronavirus 3C-like protease Dimerization Enzymatic activity Mutation Monomer |
| ISSN号 | 0042-6822 |
| DOI | 10.1016/j.virol.2009.03.034 |
| 文献子类 | Article |
| 英文摘要 | The 3C-like protease of SARS coronavirus (SARS-CoV 3CL(pro)) is vital for SARS-CoV replication and is a promising drug target. It has been extensively proved that only the dimeric enzyme is active. Here we discovered that two adjacent mutations (Ser139_Ala and Phe 140_Ala) on the dimer interface resulted in completely different crystal structures of the enzyme, demonstrating the distinct rates of these two residues in maintaining the active conformation of SARS-CoV 3CL(pro). S139A is a monomer that is structurally similar to the two reported monomers G11A and R298A. However, this mutant still retains a small fraction of dimer in solution, which might account for its remaining activity. F140A is a dimer with the most collapsed active pocket discovered so far, well-reflecting the stabilizing role of this residue. Moreover, a plausible dimerization mechanism was also deduced from structural analysis. Our work is expected to provide insight on the dimerization-function relationship of SARS-CoV 3CL(pro). (c) 2009 Elsevier Inc. All rights reserved. |
| WOS关键词 | ACUTE-RESPIRATORY-SYNDROME ; PAPAIN-LIKE PROTEASE ; MOLECULAR-DYNAMICS SIMULATIONS ; COV MAIN PROTEINASE ; DEUBIQUITINATING ACTIVITY ; EXTRA DOMAIN ; ENZYME ; DIMERIZATION ; IDENTIFICATION ; PURIFICATION |
| 资助项目 | SARS Diagnostics and Antivirals (SEPSDA)[003831] ; Foundation of Chinese Academy of Sciences[KSCX2-YW-R-18] |
| WOS研究方向 | Virology |
| 语种 | 英语 |
| WOS记录号 | WOS:000266621400011 |
| 出版者 | ACADEMIC PRESS INC ELSEVIER SCIENCE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279213]  |
| 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 药物化学研究室 药理学第三研究室 |
| 通讯作者 | Jiang, Hualiang |
| 作者单位 | 1.Chinese Acad Sci, State Key Lab Mol Biol, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China 2.Chinese Acad Sci, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Hu, Tiancen,Zhang, Yu,Li, Lianwei,et al. Two adjacent mutations on the dimer interface of SARS coronavirus 3C-like protease cause different conformational changes in crystal structure[J]. VIROLOGY,2009,388(2):324-334. |
| APA | Hu, Tiancen.,Zhang, Yu.,Li, Lianwei.,Wang, Kuifeng.,Chen, Shuai.,...&Shen, Xu.(2009).Two adjacent mutations on the dimer interface of SARS coronavirus 3C-like protease cause different conformational changes in crystal structure.VIROLOGY,388(2),324-334. |
| MLA | Hu, Tiancen,et al."Two adjacent mutations on the dimer interface of SARS coronavirus 3C-like protease cause different conformational changes in crystal structure".VIROLOGY 388.2(2009):324-334. |
入库方式： OAI收割
来源：上海药物研究所
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