Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase A subgroup
Peptidase M14 Carboxypeptidase (CP) A (CPA) belongs to the A/B subfamily of the M14 family of metallocarboxypeptidases (MCPs). The M14 family are zinc-binding CPs which hydrolyze single, C-terminal amino acids from polypeptide chains, and have a recognition site for the free C-terminal carboxyl group, which is a key determinant of specificity. CPA enzymes generally favor hydrophobic residues. A/B subfamily enzymes are normally synthesized as inactive precursors containing preceding signal peptide, followed by a globular N-terminal pro-region linked to the enzyme; these proenzymes are called procarboxypeptidases. The procarboxypeptidase A (PCPA) is produced by the exocrine pancreas and stored as a stable zymogen in the pancreatic granules until secretion into the digestive tract occurs. This subfamily includes CPA1, CPA2 and CPA4 forms. Within these A forms, there are slightly different specificities, with CPA1 preferring aliphatic and small aromatic residues, and CPA2 preferring the bulkier aromatic side chains. CPA4, detected in hormone-regulated tissues, is thought to play a role in prostate cancer.
Comment:Metallocarboxypeptidases share the zinc binding motif HXXE...H, where the zinc ion is penta-coordinated to ND1 atoms of the histidines, OE1 and OE2 atoms of the glutamic acid, and to a water molecule in a slightly distorted tetrahedral manner.
Structure:1DTD_A: human Carboxypeptidase A2; contact distance 3.5A - View structure with Cn3D
Jiyao W et al.(2023). "The conserved domain database in 2023.",