Quaternary structure, substrate selectivity and inhibitor design for SARS 3C-like proteinase

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	Quaternary structure, substrate selectivity and inhibitor design for SARS 3C-like proteinase
	Lai, Luhua ; Han, Xiaofeng ; Chen, Hao ; Wei, Ping ; Huang, Changkang ; Liu, Shiyong ; Fan, Keqiang ; Zhou, Lu ; Liu, Zhenming ; Pei, Jianfeng
刊名	CURRENT PHARMACEUTICAL DESIGN
	2006
卷号	12 期号:35 页码:4555-4564
关键词	Sars 3c-like Proteinase Quaternary Structure Enzyme Catalytic Mechanism Substrate Selectivity Inhibitor Design
ISSN号	1381-6128
英文摘要	The SARS coronavirus 3C-like proteinase is recognized as a potential drug design target for the treatment of severe acute respiratory syndrome. In the past few years, much work has been done to understand the catalytic mechanism of this target protein and to design its selective inhibitors. The protein exists as a dimer/monomer mixture in solution and the dimer was confirmed to be the active species for the enzyme reaction. Quantitative dissociation constants have been reported for the dimer by using analytic ultracentrifuge, gel filtration and enzyme assays. Though the enzyme is a cysteine protease with a chymotrypsin fold, SARS 3C-like proteinase follows the general base catalytic mechanism similar to chymotrypsin. As the enzyme can cut eleven different sites on the viral polyprotein, the substrate specificity has been studied by synthesized peptides corresponding or similar to the cleavage sites on the polyprotein. Predictive model was built for substrate structure and activity relationships and can be applied in inhibitor design. Due to the lack of potential drugs for the treatment of SARS, the discovery of inhibitors against SARS 3C-like proteinase, which can potentially be optimized as drugs appears to be highly desirable. Various groups have been working on inhibitor discovery by virtual screening, compound library screening, modification of existing compounds or natural products. High-throughput in vitro assays, auto-cleavage assays and viral replication assays have been developed for inhibition activity tests. Inhibitors with IC50 values as low as 60 nM have been reported.
语种	英语
出版者	BENTHAM SCIENCE PUBL LTD
WOS记录号	WOS:000242919900003
内容类型	期刊论文
源URL	[http://ir.iccas.ac.cn/handle/121111/58515]
专题	中国科学院化学研究所
通讯作者	Lai, Luhua
作者单位	1.Peking Univ, Coll Chem & Mol Engn, State Key Lab Struct Chem Unstable & Stable Speci, Beijing 100871, Peoples R China 2.Peking Univ, Ctr Theoret Biol, Beijing 100871, Peoples R China
推荐引用方式 GB/T 7714	Lai, Luhua,Han, Xiaofeng,Chen, Hao,et al. Quaternary structure, substrate selectivity and inhibitor design for SARS 3C-like proteinase[J]. CURRENT PHARMACEUTICAL DESIGN,2006,12(35):4555-4564.
APA	Lai, Luhua.,Han, Xiaofeng.,Chen, Hao.,Wei, Ping.,Huang, Changkang.,...&Liu, Ying.(2006).Quaternary structure, substrate selectivity and inhibitor design for SARS 3C-like proteinase.CURRENT PHARMACEUTICAL DESIGN,12(35),4555-4564.
MLA	Lai, Luhua,et al."Quaternary structure, substrate selectivity and inhibitor design for SARS 3C-like proteinase".CURRENT PHARMACEUTICAL DESIGN 12.35(2006):4555-4564.