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

来源：

JOURNAL OF MOLECULAR BIOLOGY | 1999年 / 289卷 / 02期

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.

引用

页码：371 / 384

页数：14

共 57 条

[1] CONFIRMATION OF THE ASSIGNMENT OF THE LOW-FIELD PROTON-RESONANCE OF SERINE PROTEASES BY USING SPECIFICALLY N-15 LABELED ENZYME [J].