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.