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 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.
Love
R A
RA
Agouron Pharmaceuticals, Inc., San Diego, California 92121, USA.
Parge
H E
HE
Wickersham
J A
JA
Hostomsky
Z
Z
Habuka
N
N
Moomaw
E W
EW
Adachi
T
T
Hostomska
Z
Z
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
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