the two carboxylate oxygens of glutamate-72, and a water molecule to form a distorted tetrahedral. However, once ligand binds at the active site of carboxypeptidase A, this coordination number can vary from five to six. When bound to dipeptide glycyl-L-tyrosine, the amino nitrogen of the dipeptide and the carbonyl oxygen replaced the water ligand. This would yield a coordination number of six for the zinc in the carboxypeptidase A- dipeptide glycyl-L-tyrosine complex. Electron density maps gave evidence that the amino nitrogen occupies a second position near glutamate-270. The closeness of these two residues would result in a steric hindrance preventing the water ligand from coordinating with zinc. This would result in a coordination number of five. Data for both are substantial, indicating that both situations occur naturally. There are two proposed mechanisms for the catalytic function of carboxypeptidase A. The first is a nucleophilic pathway involving a covalent acyl enzyme intermediate containing active site base Glu-270. Evidence for this anhydride intermediate is mixed; Suh and colleagues isolated what is assumed to by the acyl intermediate. However, confirmation of the acyl enzyme was done without trapping experiments, making the conclusions weak. The second proposed mechanism is a promoted water pathway. This mechanism involves attack of a water molecule at the scissile peptide linkage of the substrate. This process is promoted by the zinc ion and assisted by residue Glu-270. See also Carboxypeptidase A inhibitor Carboxypeptidase B Carboxypeptidase Carboxypeptidase E References External links The MEROPS online database for peptidases and their inhibitors: M14.001 Proteins EC 3.4.17 Metabolism Zinc enzymes