title: Avian retroviral protease and cellular aspartic proteases are distinguished by activities on peptide substrates.
abstract: The avian sarcoma/leukemia virus protease (PR), purified from avian myeloblastosis virus has a native molecular mass of 26 kDa, suggesting a dimer structure. The enzymatic activity of PR has been characterized using synthetic peptide substrates. PR is most active at pH 5.5, 35 degrees C and 2-3 M NaCl. Under these conditions PR cleaves decapeptides which are resistant in low ionic strength. This high, nonphysiological, salt concentration also increases the proteolytic activity of a cellular aspartic protease, pepsin. PR and pepsin show additional similarities: they both cleave a synthetic decapeptide at the same Tyr-Pro bond in low and high salt, while the cleavage site preferences of human renin and cathepsin-D in this substrate are altered at high salt concentrations. In addition, iodination of the tyrosine residue in this decapeptide causes an increase in the rates of hydrolysis by both PR and pepsin. However, Km values are too high to be estimated accurately for PR using Tyr-Pro and Tyr(I)-Pro decapeptides as substrates. Comparison of the digestion products of two additional decapeptides, altered in a single amino acid residue, shows that PR cleaves at fewer sites than all three cellular enzymes. Furthermore pepstatin, a strong inhibitor of pepsin, renin, and cathepsin-D has little effect on PR.
authors.affiliation: Fox Chase Cancer Center, Institute for Cancer Research, Philadelphia, Pennsylvania 19111.
authors.forename: M
authors.initials: M
authors.lastname: Kotler
authors.forename: W
authors.initials: W
authors.lastname: Danho
authors.forename: R A
authors.initials: RA
authors.lastname: Katz
authors.forename: J
authors.initials: J
authors.lastname: Leis
authors.forename: A M
authors.initials: AM
authors.lastname: Skalka
mesh_terms: D001354:Avian Leukosis Virus / Q000201:enzymology*; D009189:Avian Myeloblastosis Virus / Q000201:enzymology*; D020789:Cathepsin C; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D046911:Macromolecular Substances; D008970:Molecular Weight; D009842:Oligopeptides / Q000378:metabolism; D009994:Osmolar Concentration; D010434:Pepsin A / Q000378:metabolism*; D010436:Pepstatins / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism*; D011392:Proline / Q000378:metabolism; D011480:Protease Inhibitors; D012083:Renin / Q000378:metabolism; D012965:Sodium Chloride / Q000494:pharmacology; D013379:Substrate Specificity; D014443:Tyrosine / Q000378:metabolism
chemical_list: D046911:Macromolecular Substances; D009842:Oligopeptides; D010436:Pepstatins; D010446:Peptide Fragments; D011480:Protease Inhibitors; C014195:Streptomyces pepsin inhibitor; D014443:Tyrosine; D012965:Sodium Chloride; D011392:Proline; D010447:Peptide Hydrolases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D020789:Cathepsin C; D010434:Pepsin A; D012083:Renin; C031375:pepstatin