ABSTRACT
Carboxypeptidases cleave a single amino acid at a time from the C-terminus of peptide or protein substrates. The mammalian zinc carboxypeptidases comprise a family of enzymes with eight known members: carboxypeptidases A, A2, B, H, M, N, U and mast cell carboxypeptidase A. Within this group, the enzymes can be divided by their substrate specificities into two classes: carboxypeptidase A-like enzymes which preferentially cleave C-terminal hydrophobic residues, and carboxypeptidase B-like enzymes that cleave only the C-terminal basic residues arginine or lysine. The carboxypeptidases can also be divided into two groups according to their sequence similarities: 1) Carboxypeptidases A, B, U and mast cell carboxypeptidase A; and 2) Carboxypeptidases H, M and N. Sequence identities of enzymes within each group range from 40-58% while between groups the identity is only 14-20%. Nevertheless, many of the active site residues identified in carboxypeptidases A and B have been preserved among all of the carboxypeptidases. These include the three residues that bind the essential zinc cofactor, of which the first two (His, Glu) are separated by only two amino acids whereas the third (His) is 103-130 residues away in the linear sequence. The carboxypeptidases are widely distributed, being found in the pancreas and digestive tract (carboxypeptidases A and B), secretory granules of endocrine and neuroendocrine cells (carboxypeptidase H), plasma membranes of many cell types (carboxypeptidase M), blood (carboxypeptidase N and carboxypeptidase U) and mast cell granules (mast cell carboxypeptidase A). Although much remains to be learned about their involvement in physiological and pathophysiological processes, some important functions have been identified. These include digestion and assimilation of dietary proteins, processing of peptide hormone precursors, regulation of peptide hormone activity and regulation of protein binding.
