title: Activation of the adenovirus protease requires sequence elements from both ends of the activating peptide.
abstract: The adenovirus protease requires activation by an 11-residue peptide, GVQSLKRRRCF, to achieve maximum proteolytic activity. Derived from the C terminus of the viral protein pVI, the activating peptide (pVI-CT) forms a disulfide bond with cysteine 104 of the protease and causes a conformational change that accompanies the development of proteolytic activity. Results presented here show that the interaction of pVI-CT with the protease is dependent not only on the cysteine 10 but also on glycine 1 and valine 2. Removal of these residues, acetylation of the N-terminal glycine, or mutation of the valine to alanine or threonine significantly reduces or abolishes activation. Peptides lacking Gly-1 and Val-2 still form a disulfide bond with the protease but do not cause a conformational change in the protease also they are not effective inhibitors of activation as the interaction is readily reversed by full-length pVI-CT. These results suggest that pVI-CT causes activation by binding to two distinct regions of the protease and in doing so stabilizes the catalytic site. The reversible nature of the activation, suggested by the results presented here, may well reflect an in vivo regulatory mechanism.
authors.affiliation: Division of Cell and Molecular Biology, University of St. Andrews, Irvine Building, North Street, St. Andrews KY16 9AL, Scotland.
authors.forename: G
authors.initials: G
authors.lastname: Cabrita
authors.forename: M
authors.initials: M
authors.lastname: Iqbal
authors.forename: H
authors.initials: H
authors.lastname: Reddy
authors.forename: G
authors.initials: G
authors.lastname: Kemp
mesh_terms: D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004789:Enzyme Activation; D005998:Glycine; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship; D014633:Valine; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D010446:Peptide Fragments; D014764:Viral Proteins; C105093:glycyl-valyl-glutaminyl-seryl-leucyl-lysyl-arginyl-arginyl-arginyl-cysteinyl-phenylalanine; D003546:Cysteine Endopeptidases; C091827:adenain; D014633:Valine; D005998:Glycine