The Mode of Action of the Metal-Peptidases

Abstract

A theory of peptidase action was presented and supported by evidence bearing on 3 primary postulates: (1) that the formation of an enzyme-substrate complex consisted in the formation of a compound with definite chemical bonds; (2) that in the metal-containing peptidases at least 2 of these bonds between the substrate and the enzyme were formed through the metal (additional linkages might exist); and (3) that the 2 linkages formed between the metal and the substrate were on opposite sides of the peptide bond. It was argued that these 2 strong linkages contributed to an electronic distortion at the peptide bond and that this labilization (decrease in energy of ac-tivation) permitted the usual catalytic hydrolysis of the linkage by hydrogen or hydroxyl ions.