title: The tryptic activation pathway of monomeric procarboxypeptidase A.
abstract: Procarboxypeptidases are the remaining major digestive zymogens the activation process of which remains unsolved. Here it is shown that in the tryptic activation of monomeric procarboxypeptidase A from porcine pancreas, the generation of carboxypeptidase A (CPA) activity parallels the limited proteolysis of the 94-residue activation segment. This degradation proceeds from the COOH-terminal end of the molecule, and CPA itself makes an important and unexpected contribution by excising the COOH-terminal arginine residue of the released primary activation fragment. Successive cleavages at some of the peptide bonds of the activation segment nearest to the COOH terminus were found to be of prime importance in eliciting CPA activity, particularly those involving the carbonyl groups of Arg94 and Gly93 which were first cleaved. It is also shown that the rate of activation does not depend directly upon the generation of CPA-alpha and its conversion to CPA-beta.
authors.affiliation: Departament de Bioquímica i Biologia Molecular (Facultat de Ciències), Universitat Autònoma de Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Vendrell
authors.forename: C M
authors.initials: CM
authors.lastname: Cuchillo
authors.forename: F X
authors.initials: FX
authors.lastname: Avilés
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002268:Carboxypeptidases / Q000378:metabolism*; D043422:Carboxypeptidases A; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism*; D007700:Kinetics; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000302:isolation & purification; D010449:Peptide Mapping; D011487:Protein Conformation; D013379:Substrate Specificity; D013552:Swine; D014357:Trypsin / Q000378:metabolism*
chemical_list: D004792:Enzyme Precursors; D010446:Peptide Fragments; D002268:Carboxypeptidases; D043422:Carboxypeptidases A; D014357:Trypsin