Viral cysteine proteases are homologous to the trypsin-like family of serine proteases: structural and functional implications

Proc Natl Acad Sci U S A. 1988 Nov;85(21):7872-6. doi: 10.1073/pnas.85.21.7872.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cysteine Endopeptidases / analysis*
  • Molecular Sequence Data
  • Picornaviridae / enzymology*
  • Plants
  • Sequence Homology, Nucleic Acid
  • Serine Endopeptidases / analysis*
  • Structure-Activity Relationship

Substances

  • Serine Endopeptidases
  • Cysteine Endopeptidases