Carboxypeptidase A

Carboxypeptidase A is a digestive enzyme that hydrolyzes the carboxyl-terminal peptide bond in polypeptide chains.

Amino Acid

Hydrolysis occurs most readily if the carboxyl-terminal residue has an aromatic or a bulky aliphatic side chain. (Stryer,1988)

The enzyme serves as a good illustration of protein secondary structure. The single polypeptide chain of 307 amino acids contains regions of alpha helix (385) and beta pleated sheet (17%).

Carboxypeptidase A also demonstrates two important catalytic mechanisms :

induced fit
electronic strain

Binding of a typical substrate such as glycyl-tyrosine results in a structural rearrangement of the active site (induced fit). Residues which are thought to interact with the substrate include Glutamate 270, Arginine 145, Arginine 127, and Tyrosine 248.

A zinc atom is coordinated in a tetrahedral array with the amino acids Histidine 69, Histidine 196, and Glutamate 72, and either a water or substate molecule. The zinc atom is a prosthetic group that is essential for enzymatic activity and is largely responsible for the electronic strain created at the active site. In the illustration below, zinc polarizes the carbonyl group of the peptide bond in glycyl-tyrosine, making it more susceptible to attack by Glutamate 270.

Amino Acid

(Stryer,1988)