The crystal structure of hepatitis C virus NS3 proteinase reveals a trypsin-like fold and a structural zinc binding site

Cell. 1996 Oct 18;87(2):331-42. doi: 10.1016/s0092-8674(00)81350-1.

Abstract

During replication of hepatitis C virus (HCV), the final steps of polyprotein processing are performed by a viral proteinase located in the N-terminal one-third of nonstructural protein 3. The structure of NS3 proteinase from HCV BK strain was determined by X-ray crystallography at 2.4 angstrom resolution. NS3P folds as a trypsin-like proteinase with two beta barrels and a catalytic triad of His-57, Asp-81, Ser-139. The structure has a substrate-binding site consistent with the cleavage specificity of the enzyme. Novel features include a structural zinc-binding site and a long N-terminus that interacts with neighboring molecules by binding to a hydrophobic surface patch.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Crystallography, X-Ray
  • Hepatitis C / enzymology*
  • Metalloproteins / ultrastructure
  • Models, Molecular
  • Molecular Sequence Data
  • Recombinant Proteins
  • Sequence Alignment
  • Trypsin
  • Viral Nonstructural Proteins / ultrastructure*
  • Zinc

Substances

  • Metalloproteins
  • NS3 protein, hepatitis C virus
  • Recombinant Proteins
  • Viral Nonstructural Proteins
  • Trypsin
  • Zinc