Residues on the dimer interface of SARS coronavirus 3C-like protease: Dimer stability characterization and enzyme catalytic activity analysis

doi:10.1093/jb/mvm246

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药物发现与设计中心

	Residues on the dimer interface of SARS coronavirus 3C-like protease: Dimer stability characterization and enzyme catalytic activity analysis
	Chen, Shuai; Zhang, Jian; Hu, Tiancen; Chen, Kaixian; Jiang, Hualiang; Shen, Xu
刊名	JOURNAL OF BIOCHEMISTRY
	2008-04
卷号	143 期号:4 页码:525-536
关键词	catalytic mechanism dimerization-activity relationship dimer interface residue-residue interactions site-directed mutagenesis
ISSN号	0021-924X
DOI	10.1093/jb/mvm246
文献子类	Article
英文摘要	3C-like protease (3CL(pro)) plays pivotal roles in the life cycle of severe acute respiratory syndrome coronavirus (SARS-CoV) and only the dimeric protease is proposed as the functional form. Guided by the crystal structure and molecular dynamics simulations, we performed systematic mutation analyses to identify residues critical for 3CL(pro) dimerization and activity in this study. Seven residues on the dimer interface were selected for evaluating their contributions to dimer stability and catalytic activity by biophysical and biochemical methods. These residues are involved in dimerization through hydrogen bonding and broadly located in the N-terminal finger, the alpha-helix A' of domain I, and the oxyanion loop near the S1 substrate-binding subsite in domain II. We revealed that all seven single mutated proteases still have the dimeric species but the monomer-dimer equilibria of these mutants vary from each other, implying that these residues might contribute differently to the dimer stability. Such a conclusion could be further verified by the results that the proteolytic activities of these mutants also decrease to varying degrees. The present study would help us better understand the dimerization-activity relationship of SARS-CoV 3CL(pro) and afford potential information for designing anti-viral compounds targeting the dimer interface of the protease.
WOS关键词	ACUTE RESPIRATORY SYNDROME ; MOLECULAR-DYNAMICS SIMULATIONS ; VIRUS-ENCODED PROTEINASES ; MAIN PROTEINASE ; EXTRA DOMAIN ; INHIBITOR ; DIMERIZATION ; PURIFICATION ; EXPRESSION ; SUBSTRATE
WOS研究方向	Biochemistry & Molecular Biology
语种	英语
出版者	OXFORD UNIV PRESS
WOS记录号	WOS:000255957500010
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272948]
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理学第三研究室
通讯作者	Shen, Xu
作者单位	Chinese Acad Sci, Shanghai Inst Materia Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Chen, Shuai,Zhang, Jian,Hu, Tiancen,et al. Residues on the dimer interface of SARS coronavirus 3C-like protease: Dimer stability characterization and enzyme catalytic activity analysis[J]. JOURNAL OF BIOCHEMISTRY,2008,143(4):525-536.
APA	Chen, Shuai,Zhang, Jian,Hu, Tiancen,Chen, Kaixian,Jiang, Hualiang,&Shen, Xu.(2008).Residues on the dimer interface of SARS coronavirus 3C-like protease: Dimer stability characterization and enzyme catalytic activity analysis.JOURNAL OF BIOCHEMISTRY,143(4),525-536.
MLA	Chen, Shuai,et al."Residues on the dimer interface of SARS coronavirus 3C-like protease: Dimer stability characterization and enzyme catalytic activity analysis".JOURNAL OF BIOCHEMISTRY 143.4(2008):525-536.