Two adjacent mutations on the dimer interface of SARS coronavirus 3C-like protease cause different conformational changes in crystal structure

	Two adjacent mutations on the dimer interface of SARS coronavirus 3C-like protease cause different conformational changes in crystal structure
	Hu, TC; Zhang, Y; Li, LW; Wang, KF; Chen, S; Chen, J; Ding, JP; Jiang, HL; Shen, X
刊名	VIROLOGY
	2009
卷号	388 期号:2 页码:324-334
关键词	SARS coronavirus 3C-like protease Dimerization Enzymatic activity Mutation Monomer
通讯作者	Jiang, HL (reprint author), Chinese Acad Sci, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai Inst Mat Med, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China.,hljiang@mail.shcnc.ac.cn ; xshen@mail.shcnc.ac.cn
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.
学科主题	Virology
类目[WOS]	Virology
关键词[WOS]	ACUTE-RESPIRATORY-SYNDROME ; PAPAIN-LIKE PROTEASE ; MOLECULAR-DYNAMICS SIMULATIONS ; COV MAIN PROTEINASE ; DEUBIQUITINATING ACTIVITY ; EXTRA DOMAIN ; ENZYME ; DIMERIZATION ; IDENTIFICATION ; PURIFICATION
收录类别	SCI
语种	英语
WOS记录号	WOS:000266621400011
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1144]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Hu, TC,Zhang, Y,Li, LW,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, TC.,Zhang, Y.,Li, LW.,Wang, KF.,Chen, S.,...&Shen, X.(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, TC,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.