The solution structure of the N-terminal proteinase domain of the hepatitis C virus (HCV) NS3 protein provides new insights into its activation and catalytic mechanism

被引:102
作者
Barbato, G [1 ]
Cicero, DO [1 ]
Nardi, MC [1 ]
Steinkühler, C [1 ]
Cortese, R [1 ]
De Francesco, R [1 ]
Bazzo, R [1 ]
机构
[1] Ist Ric Biol Mol P Angeletti, I-00040 Pomezia, Italy
关键词
HCV; NS3; serine proteinase; structure; NMR;
D O I
10.1006/jmbi.1999.2745
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The solution structure of the hepatitis C virus (BK strain) NS3 protein N-terminal domain (186 residues) has been solved by NMR spectroscopy. The protein is a serine protease with a chymotrypsin-type fold, and is involved in the maturation of the viral polyprotein. Despite the knowledge that its activity is enhanced by the action of a viral protein cofactor, NS4A, the mechanism of activation is not yet clear. The analysis of the folding in solution and the differences from the crystallographic structures allow the formulation of a model in which, in addition to the NS4A cofactor, the substrate plays an important role in the activation of the catalytic mechanism. A unique structural feature is the presence of a zinc-binding site exposed on the surface, subject to a slow conformational exchange process. (C) 1999 Academic Press.
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页码:371 / 384
页数:14
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