Viral cysteine proteases are homologous to the trypsin-like family of serine proteases: structural and functional implications.
Proteases that are encoded by animal picornaviruses and plant como- and potyviruses form a related group of cysteine-active-center enzymes that are essential for virus maturation. We show that these proteins are homologous to the family of trypsin-like serine proteases. In our model, the active-site nucleophile of the trypsin catalytic triad, Ser-195, is changed to a Cys residue in these viral proteases. The other two residues of the triad, His-57 and Asp-102, are otherwise absolutely conserved in all the viral protease sequences. Secondary structure analysis of aligned sequences suggests the location of the component strands of the twin beta-barrel trypsin fold in the viral proteases. Unexpectedly, the 2a and 3c subclasses of viral cysteine proteases are, respectively, homologous to the small and large structural subclasses of trypsin-like serine proteases. This classification allows the molecular mapping of residues from viral sequences onto related tertiary structures; we precisely identify amino acids that are strong determinants of specificity for both small and large viral cysteine proteases.
Bazan
J F
JF
Department of Biophysics, University of California, Berkeley 94720.
Fletterick
R J
RJ
D000595:Amino Acid Sequence; D003546:Cysteine Endopeptidases / Q000032:analysis*; D008969:Molecular Sequence Data; D010849:Picornaviridae / Q000201:enzymology*; D010944:Plants; D012689:Sequence Homology, Nucleic Acid; D012697:Serine Endopeptidases / Q000032:analysis*; D013329:Structure-Activity Relationship
D012697:Serine Endopeptidases; D003546:Cysteine Endopeptidases