title: New stimulation ligand of the adenovirus 2 protease.
abstract: The catalytic activity of the adenovirus cysteine peptidase is increased by a specific 11-amino-acid peptide adduct (GVQSLKRRRCF, referred to as pVIc). To identify additional peptides which might bind and alter the activity of the protease, a cysteine-constrained random peptide phage library was screened. Of 29 different phages which were isolated, 7 contained the consensus sequence VEGGS. Despite a superficial similarity to the substrate cleavage site of the protease, the peptide was not digested by the enzyme. VEGGS and pVIc altered protease activity similarly without sharing sequence similarity. To similar degrees, pVIc and VEGGS (a) stimulated the activity of the recombinant protease, (b) had no effect on viral protease, (c) increased the fluorescence emission of tryptophan residues in the protease, suggesting a conformational change, and (d) inhibited wt virus infection, but rescued ts1 infection at the nonpermissive temperature. The experiments also suggest that once the protease has been stimulated by one peptide, the other peptide has no further activity on the recombinant adenovirus cysteine protease, suggesting that the two peptides bring about the same change on the protease via different binding sites.
authors.affiliation: Department of Microbiology, Feculty of Medicine, University of Sherbrooke, Quebec, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Diouri
authors.forename: G S
authors.initials: GS
authors.lastname: Girouard
authors.forename: C M
authors.initials: CM
authors.lastname: Allen
authors.forename: S
authors.initials: S
authors.lastname: Sircar
authors.forename: J E
authors.initials: JE
authors.lastname: Van Lier
authors.forename: J M
authors.initials: JM
authors.lastname: Weber
mesh_terms: D000260:Adenoviruses, Human / Q000201:enzymology*; D000595:Amino Acid Sequence; D001435:Bacteriophages / Q000235:genetics; D001665:Binding Sites; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism; D013379:Substrate Specificity; D014364:Tryptophan; D014407:Tumor Cells, Cultured
chemical_list: D008024:Ligands; D010455:Peptides; D014364:Tryptophan; D003546:Cysteine Endopeptidases