Journal
VIROLOGY
Volume 388, Issue 2, Pages 324-334Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2009.03.034
Keywords
SARS coronavirus; 3C-like protease; Dimerization; Enzymatic activity; Mutation; Monomer
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Funding
- SARS Diagnostics and Antivirals (SEPSDA) [003831]
- Foundation of Chinese Academy of Sciences [KSCX2-YW-R-18]
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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.
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