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

JOURNAL OF MOLECULAR BIOLOGY

卷:289

Article

Barbato, G ; Cicero, DO ; Nardi, MC ; Steinkühler, C ; Cortese, R ; De Francesco, R ; Bazzo, R

关键词: HCV;    NS3;    serine proteinase;    structure;    NMR;   

DOI  :  10.1006/jmbi.1999.2745

来源: Elsevier

【 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.

【 授权许可】

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