Carboxypeptidase A2 (CPA2)

Carboxypeptidase A2 (CPA2) is a **zinc-dependent metalloprotease enzyme** primarily expressed and secreted by the human pancreas as a digestive enzyme[3][7]. It catalyzes the hydrolysis of the C-terminal amino acid from dietary peptides, showing a *substrate preference for large aromatic residues* (such as tryptophan, phenylalanine, tyrosine)[3][7]. The enzyme is synthesized as an inactive zymogen (procarboxypeptidase A2) and activated in the small intestine via proteolytic cleavage, primarily by trypsin, which removes the inhibitory pro-segment[1][3]. CPA2 belongs to the M14 family of metallocarboxypeptidases and is a structurally distinct isoform compared to CPA1 and CPA3[1]. Mutations or dysregulation in CPA2 have been associated with pancreatitis and rare parasitic diseases such as gnathomiasis[4]. There is interest in CPA2 as a biotechnological tool for *antibody–directed prodrug therapy* in cancer due to its well-characterized substrate specificity and ability to activate certain prodrugs at target sites[1]. No approved pharmaceuticals target CPA2 directly for therapeutic inhibition; small molecule inhibitors have been developed for biochemical studies, and CPA2’s physiological role in digestion suggests potential safety concerns if systemically inhibited.

Other names

Carboxypeptidase A2, pancreaticCPA2Procarboxypeptidase A2CBPA2Carboxypeptidase A2 (pancreatic)

Competitive inhibition of peptide/ester hydrolysis (e.g., by small molecule inhibitors such as benzylsuccinic acid); chelation of active-site Zn²⁺ prevents enzymatic activity[1]