The severed activation segment of porcine pancreatic procarboxypeptidase A is a powerful inhibitor of the active enzyme. Isolation and characterisation of the activation peptide.
The activation peptide of the monomeric procarboxypeptidase A from porcine pancreas was isolated by means of controlled trypsin digestion of the proenzyme followed by ion-exchange chromatography under dissociating conditions (7 M urea). The molecular weight of the isolated peptide was estimated to be around 11500-12000 (corresponding to approx. 100-103 residues) as judged by SDS electrophoresis and amino acid analysis, a figure that agrees with the differences between the corresponding values for procarboxypeptidase A and carboxypeptidase A (peptidyl-L-amino acid hydrolase, EC 3.4.17.1). The activation peptide has a high content of hydrophobic and acidic amino acids, and lacks cysteine. A remarkable feature is the strong competitive inhibitory action of the peptide on both porcine and bovine pancreatic carboxypeptidase A activity, with a Ki in the nanomolar range, and its null ability to inhibit porcine pancreatic carboxypeptidase B (EC 3.4.17.2). The above properties, and the fact that the peptide has the same N-terminal residue (lysine) as the parent procarboxypeptidase A, suggest that the isolated peptide contains most (if not all) of the activation segment of the proenzyme.
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D043422:Carboxypeptidases A; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000494:pharmacology*; D007700:Kinetics; D008970:Molecular Weight; D010179:Pancreas / Q000201:enzymology; D010446:Peptide Fragments / Q000032:analysis; D013552:Swine
D000596:Amino Acids; D004792:Enzyme Precursors; D010446:Peptide Fragments; D002268:Carboxypeptidases; D043422:Carboxypeptidases A