Hydrolysis Of Polypeptides Research Articles

THE STRUCTURE OF CARBOXYPEPTIDASE A, VI. SOME RESULTS AT 2.0-Å RESOLUTION, AND THE COMPLEX WITH GLYCYL-TYROSINE AT 2.8-Å RESOLUTION

Bovine carboxypeptidase A, (CPA) is a zinc-containing enzyme of mol wt 34,600 which catalyzes the hydrolysis of polypeptides at the C-terminal peptide bond, especially if the terminal residue of the substrate is aromatic. We have extended our X-ray diffraction study of CPA1-4 to 2.0-A resolution and the study of its complex with glycyl-L-tyrosine to 2.8 A. A detailed examination of the course of the polypeptide chain shows that the molecule is composed of several helical regions, a large central twisted sheet of eight extended chains with considerable P-structure, and a tortuously folded coil. We have located published portions of the amino acid sequence at the N-terminus, the C-terminus, the two cysteinyl residues, and the active tyrosyl residue. We also describe the protein side chains which are near the bound Gly-Tyr and the large conformational changes which occur in the presence of this substrate.

Mechanism of the Acid Hydrolysis of Glycylglycine

NUMEROUS studies have been made on the hydrolysis of polypeptides for the determination of the composition of proteins. Usually these hydrolyses are conducted in acid solution. The kinetics of the acid hydrolysis of some dipeptides has been studied by Synge1 and Lawrence and Moore2; but no mechanism has been suggested. However, in the acid hydrolysis of the amides, Benrath3 and Euler and Olander4 have reached the conclusion that it is the amide cation which hydrolyses. Ingold5 states that the rate-controlling step is a bimolecular reaction between a water molecule and the amide cation.