title: The crystal structure of hepatitis C virus NS3 proteinase reveals a trypsin-like fold and a structural zinc binding site.
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.
authors.affiliation: Agouron Pharmaceuticals, Inc., San Diego, California 92121, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Love
authors.forename: H E
authors.initials: HE
authors.lastname: Parge
authors.forename: J A
authors.initials: JA
authors.lastname: Wickersham
authors.forename: Z
authors.initials: Z
authors.lastname: Hostomsky
authors.forename: N
authors.initials: N
authors.lastname: Habuka
authors.forename: E W
authors.initials: EW
authors.lastname: Moomaw
authors.forename: T
authors.initials: T
authors.lastname: Adachi
authors.forename: Z
authors.initials: Z
authors.lastname: Hostomska
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006526:Hepatitis C / Q000201:enzymology*; D008667:Metalloproteins / Q000648:ultrastructure; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011994:Recombinant Proteins; D016415:Sequence Alignment; D014357:Trypsin; D017361:Viral Nonstructural Proteins / Q000648:ultrastructure*; D015032:Zinc; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D008667:Metalloproteins; D011994:Recombinant Proteins; D014357:Trypsin; D017361:Viral Nonstructural Proteins; D015032:Zinc; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases