Carboxypeptidase

Carboxypeptidase A, from bovine pancreas

Carboxypeptidases are a type of protease enzyme (EC number 3.4.16 - 3.4.18) that function to hydrolyze or cleave peptide bonds at the carboxy-terminal (C-terminal) of proteins or peptides. This contrasts with aminopeptidase enzymes, which act on the opposite end of the protein. Found in humans, animals, and plants, carboxypeptidases have an array of functions from catabolism to the maturation of proteins.

Functions

While early studies on carboxypeptidases focused on their role in food digestion (like pancreatic carboxypeptidases A1, A2, and B), it's now known that most carboxypeptidases have functions beyond catabolism. These enzymes:

• Aid in protein maturation
• Facilitate the biosynthesis of neuroendocrine peptides, such as insulin
• Play roles in blood clotting, growth factor production, wound healing, reproduction, and numerous other biological processes

Classification

By Active Site Mechanism

Carboxypeptidases can be grouped based on their active site mechanism:

• Metallo-carboxypeptidases (EC number 3.4.17): Use a metal in their active site
• Serine carboxypeptidases (EC number 3.4.16): Use active site serine residues
• Cysteine carboxypeptidases or thiol carboxypeptidases (EC number 3.4.18): Utilize an active site cysteine

Note: These classifications are not about the selectivity of the amino acid cleavage.

By Substrate Preference

Based on substrate preference, carboxypeptidases can be further categorized as:

• Carboxypeptidase A: Prefers amino acids with aromatic or branched hydrocarbon chains (A for aromatic/aliphatic)
• Carboxypeptidase B: Acts on positively charged amino acids like arginine and lysine (B for basic)
• Glutamate carboxypeptidase: A metallo-carboxypeptidase that cleaves C-terminal glutamate from N-acetyl-L-aspartyl-L-glutamate peptides
• Prolyl carboxypeptidase: A serine carboxypeptidase that cleaves the C-terminal residue from peptides with the sequence -Pro-Xaa (where Pro represents proline and Xaa any C-terminus amino acid)

Activation

Some carboxypeptidases are synthesized as inactive precursors known as procarboxypeptidases. For instance, pancreatic carboxypeptidase A starts as an inactive zymogen - pro-carboxypeptidase A, which is then activated to carboxypeptidase A by the enzyme enteropeptidase. This process prevents self-digestion of the cells producing the pro-carboxypeptidase A.

See Also

• Carboxypeptidase E
• Carboxypeptidase A
• Enzyme category EC number 3.4
• Thrombin-activatable fibrinolysis inhibitor or plasma carboxypeptidase B2
• bacterial transpeptidase, an alanine carboxypeptidase
• bradykinin undergoes degradation by carboxypeptidase N, among other enzymes
• D-Ala carboxypeptidase is a type of penicillin-binding protein
• Phenylalanine may act as an inhibitor for carboxypeptidase A