THE CRYSTAL-STRUCTURE OF HEPATITIS-C VIRUS NS3 PROTEINASE REVEALS A TRYPSIN-LIKE FOLD AND A STRUCTURAL ZINC-BINDING SITE

During replication of hepatitis C virus (HCV), the final steps of poly protein 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 trypsinlike proteinase wit h two beta barrels and a catalytic triad of His-57, Asp-81, Ser-139. T he structure has a substrate-binding site consistent with the cleavage specificity of the enzyme. Novel features include a structural zinc-b inding site and a long N-terminus that interacts with neighboring mole cules by binding to a hydrophobic surface patch.