Carboxypeptidase A usually refers to the pancreatic exopeptidase that hydrolyzes peptide bonds of C-terminal residues with aromatic or aliphatic side-chains. Most scientists in the field now refer to this enzyme as CPA1, and to a related pancreatic carboxypeptidase as CPA2. Types In addition, there are 4 other mammalian enzymes named CPA-3 through CPA-6, and none of these are expressed in the pancreas. Instead, these other CPA-like enzymes have diverse functions. CPA3 (also known as mast-cell CPA) is involved in the digestion of proteins by mast cells. CPA4 (previously known as CPA-3, but renumbered when mast-cell CPA was designated CPA-3) may be involved in tumor progression, but this enzyme has not been well studied. CPA5 has not been well studied. CPA6 is expressed in many tissues during mouse development, and in adult shows a more limited distribution in brain and several other tissues. CPA6 is present in the extracellular matrix where it is enzymatically active. A human mutation of CPA-6 has been linked to Duane's syndrome (abnormal eye movement). Recently, mutations in CPA6 were found to be linked to epilepsy. CPA6 is also one of several enzymes which degrade enkephalins. Function CPA-1 and CPA-2 (and, it is presumed, all other CPAs) employ a zinc ion within the protein for hydrolysis of the peptide bond at the C-terminal end of an amino acid residue. Loss of the zinc leads to loss of activity, which can be replaced easily by zinc, and also by some other divalent metals (cobalt, nickel). Carboxypeptidase A is produced in the pancreas and is crucial to many processes in the human body to include digestion, post-translational modification of proteins, blood clotting, and reproduction. Applications This vast scope of functionality for a single protein makes it the ideal model for research regarding other zinc proteases of unknown structure. Recent biomedical research on collagenase, enkephlinase, and angiotensin-converting enzyme used carboxypeptidase A for inhibitor synthesis and kinetic testing. For example, a drug that treats high blood pressure, Captopril, was designed based on a carboxypeptidase A inhibitor. Carboxypeptidase A and the target enzyme of Captopril, angiotensin-converting enzyme, have very similar structures, as they both contain a zinc ion within the active site. This allowed for a potent carboxypeptidase A inhibitor to be used to inhibit the enzyme and, thus, lower blood pressure through the renin-angiotensin-aldosterone system. Structure Carboxypeptidase A (CPA) contains a zinc (Zn2+) metal center in a tetrahedral geometry with amino