Carboxypeptidase

Carboxypeptidase refers to a class of exopeptidases that hydrolyze the C-terminal peptide bond of proteins and peptides, releasing a free carboxyl-terminal amino acid. Most well studied carboxypeptidases are zinc-dependent metalloproteases belonging to the M14 family. The catalytic zinc ion in the active site helps activate a water molecule that attacks the peptide carbonyl carbon, leading to bond cleavage. The active site typically features residues that coordinate zinc and contribute to catalysis, including a HEXXH-like motif common to many metalloproteases.

In humans and other organisms, carboxypeptidases show substantial diversity in localization and substrate preference. Pancreatic carboxypeptidase A and carboxypeptidase B are secreted into the small intestine during digestion; A generally prefers bulky hydrophobic C-terminal residues, while B has higher activity toward basic residues such as arginine and lysine. Other carboxypeptidases can be soluble enzymes in plasma or tissue membranes with distinct tissue distribution and substrate specificities, participating in processing or inactivation of regulatory peptides and hormones.

Function and significance: by trimming C-terminal amino acids, carboxypeptidases contribute to protein digestion, post-translational processing of peptide hormones and neuropeptides, and the regulation of bioactive peptides. They are used in biochemical research and peptide sequencing and are studied for their roles in physiology and disease. Inhibitors and modulators of carboxypeptidases can affect peptide turnover and signaling pathways, reflecting their broad biological importance.