Molecular model of the specificity pocket of the hepatitis C virus protease: implications for substrate recognition.
We have built a model of the specificity pocket of the protease of hepatitis C virus on the basis of the known structures of trypsin-like serine proteases and of the conservation pattern of the protease sequences among various hepatitis C strains. The model allowed us to predict that the substrate of this protease should have a cysteine residue in position P1. This hypothesis was subsequently proved by N-terminal sequencing of two products of the protease. The success of this "blind" test increases our confidence in the overall correctness of our proposed alignment of the enzyme sequence with those of other proteases of known structure and constitutes a first step in the construction of a complete model of the viral protease domain.
Pizzi
E
E
Istituto di Ricerche di Biologia Molecolare, Rome, Italy.
Tramontano
A
A
Tomei
L
L
La Monica
N
N
Failla
C
C
Sardana
M
M
Wood
T
T
De Francesco
R
R
D000595:Amino Acid Sequence; D001665:Binding Sites / Q000235:genetics; D006367:HeLa Cells; D016174:Hepacivirus / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D017386:Sequence Homology, Amino Acid; D012697:Serine Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity
D012697:Serine Endopeptidases