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.
Barbato, G., Cicero, D.o., Nardi, M., Steinkuhler, C., Cortese, R., De Francesco, R., et al. (1999). 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, 289, 371-384.
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
CICERO, DANIEL OSCAR;
1999-01-01
Abstract
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.File | Dimensione | Formato | |
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