Mechanism for controlling the monomer–dimer conversion of SARS coronavirus main protease

doi:10.1107/S0907444913001315

淡江大學機構典藏 > 理學院 > 化學學系暨研究所 > 期刊論文 > Item 987654321/91703

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題名:	Mechanism for controlling the monomer–dimer conversion of SARS coronavirus main protease
作者:	Wu, Cheng-Guo;Cheng, Shu-Chun;Chen, Shiang-Chuan;Li, Juo-Yan;Fang, Yi-Hsuan;Chen, Yau-Hung;Chou, Chi-Yuan
貢獻者:	淡江大學生命科學研究所
關鍵詞:	SARS;SARS coronavirus;main protease
日期:	2013-05-01
上傳時間:	2013-07-29 09:24:21 (UTC+8)
出版者:	Malden: Wiley-Blackwell Publishing, Inc.
摘要:	The Severe acute respiratory syndrome coronavirus (SARS-CoV) main protease (Mpro) cleaves two virion polyproteins (pp1a and pp1ab); this essential process represents an attractive target for the development of anti-SARS drugs. The functional unit of Mpro is a homodimer and each subunit contains a His41/Cys145 catalytic dyad. Large amounts of biochemical and structural information are available on Mpro; nevertheless, the mechanism by which monomeric Mpro is converted into a dimer during maturation still remains poorly understood. Previous studies have suggested that a C-terminal residue, Arg298, interacts with Ser123 of the other monomer in the dimer, and mutation of Arg298 results in a monomeric structure with a collapsed substrate-binding pocket. Interestingly, the R298A mutant of Mpro shows a reversible substrate-induced dimerization that is essential for catalysis. Here, the conformational change that occurs during substrate-induced dimerization is delineated by X-ray crystallography. A dimer with a mutual orientation of the monomers that differs from that of the wild-type protease is present in the asymmetric unit. The presence of a complete substrate-binding pocket and oxyanion hole in both protomers suggests that they are both catalytically active, while the two domain IIIs show minor reorganization. This structural information offers valuable insights into the molecular mechanism associated with substrate-induced dimerization and has important implications with respect to the maturation of the enzyme.
關聯:	Acta Crystallographica Section D Biological Crystallography 69(5), pp.747-755
DOI:	10.1107/S0907444913001315
顯示於類別:	[化學學系暨研究所] 期刊論文

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