Structural Biochemistry/Carboxypeptidase

Carboxypeptidase is a pancreatic enzyme that catalyzes the hydrolysis of the peptide bond at the carboxyl end of proteins and peptides, with a strong preference for amino acids with an aromatic or branched aliphatic side chain. The zinc ion is bound in a 5-coordinate site by two histidine nitrogens, both oxygens from a glutamic acid carboxyl group, and a water molecule. A pocket in the protein structure accommodates the side chain of the substrate. Evidence indicates that the negative carboxyl group of the substrate hydrogen bonds to an arginine on the enzyme while the zinc bonds to the oxygen of the peptide carbonyl. A Zn-OH or Zn-OH2 combination seems to be the group that reacts with the carbonyl carbon, with assistance of a glutamic acid carboxyl group from the enzyme that assists in the transfer of H+ from the bound water to the amino acid product. An artificial peptidase model compound has been made with a Cu(II) bound by four nitrogens in a chain that ends in a guanidinium ion, all attached to a cross-linked polystyrene. The catalytic activity is high for hydrolysis of amides with carboxyl groups attached, similar to a carboxypeptidase activity. The H+ on the guanidinium group can hydrogen-bond to the carboxyl group, holding the substrate in position near the Cu, which is the active site.


Gary L. Miessler, Donald A. Tarr, Inorganic Chemistry, Third Edition, 2004