Protein Name

Hepatitis C virus NS3 protease


Hepatitis C virus(HCV)

Biological Context

Hepatitis C viruses (HCVs), which infect about 1% of the global population, have no broadly effective treatments available, except for the interferon treatment even the effectiveness of which is limited. The HCV genome encodes a polyprotein divided into structural (envelope and core components) and nonstructural (NS) proteins (the catalytic machinery for HCV replication). Among these, NS3 protein contains a serine protease which processes the HCV polyprotein at four specific sites releasing proteins that are essential for replication. The NS3 protease domain requires to be bound to the central hydrophobic region of NS4A, another NS protein in HCV, for its stability and activation.

Structure Description


The above structure shows the complex of NS3 protease domain of HCV with a synthetic NS4A activator peptide. It has two structural domains, each with a twisted beta sheet incorporating a "Greek key" motif. It also contains a zinc-binding motif with a possible structural role. The NS3 serine protease domain adopts a chymotrypsin-like fold but lacks several loops found in other members of the chymotrypsin family. The active site is located in the N-terminal domain of the NS3 protease between the cleft separating the two domains. The authors propose that the interaction between NS3 and NS4A should be considered as a possible target for future anti-HCV drug design efforts.

Protein Data Bank (PDB)



  • Kim, J.L. Morgenstern, K.A. Lin, C. Fox, T. Dwyer, M.D. Landro, J.A. Chambers, S.P. Markland, W. Lepre, C.A. O'Malley, E.T. Harbeson, S.L. Rice, C.M. Murcko, M.A. Caron, P.R. Thomson, J.A.; "Crystal structure of the hepatitis C virus NS3 protease domain complexed with a synthetic NS4A cofactor peptide."; Cell; (1996) 87:343-355 PubMed:8861917.


Author: Ashwini Patil

Japanese version:PDB:1A1R