Two Adjacent Mutations on the Dimer Interface of SARS Coronavirus 3C-like Protease Cause Different Conformational Changes in Crystal Structure

Overview

Journal Virology

Specialty Microbiology

Date 2009 May 5

PMID 19409595

Citations 56

Authors

Tiancen Hu

Yu Zhang

Lianwei Li

Kuifeng Wang

Shuai Chen

Jing Chen

Jianping Ding

Hualiang Jiang

Xu Shen

Affiliations

Soon will be listed here.

Abstract

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 Phe140_Ala) on the dimer interface resulted in completely different crystal structures of the enzyme, demonstrating the distinct roles 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).

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