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

被引：80

作者：

Hu, Tiancen ^{[1
]}

Zhang, Yu ^{[1
]}

Li, Lianwei ^{[1
]}

Wang, Kuifeng ^{[1
]}

Chen, Shuai ^{[1
]}

Chen, Jing ^{[1
]}

Ding, Jianping ^{[2
]}

Jiang, Hualiang ^{[1
]}

Shen, Xu ^{[1
]}

机构：

[1] Chinese Acad Sci, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China

[2] Chinese Acad Sci, State Key Lab Mol Biol, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China

来源：

VIROLOGY | 2009年 / 388卷 / 02期

关键词：

SARS coronavirus; 3C-like protease; Dimerization; Enzymatic activity; Mutation; Monomer; ACUTE-RESPIRATORY-SYNDROME; PAPAIN-LIKE PROTEASE; COV MAIN PROTEINASE; DIMERIZATION; IDENTIFICATION; PURIFICATION; DISSOCIATION; CATALYSIS; ENZYME; BIOSYNTHESIS;

D O I：

10.1016/j.virol.2009.03.034

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

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.

引用

页码：324 / 334

页数：11

共 53 条

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