Molecular orbital study of proton transfer energetics in the active site of papain by using methanethiol-imidazole-formic acid complex as a model.

Abstract

The energetics of proton transfers in the methanethiol-imidazole-formic acid complex were analyzed from a quantum chemical point of view in order to elucidate the nature of the enzymatic reaction of papain and the electronic structure in the active site. Methanethiol, imidazole and formic acid were used as models of the side chains of Cys 25, His 159 and Asp 158. The calculations were performed within the closed-shell-LCAO-ab initio MO method by using a 4-31G basis set. The hydrogen-bonding structure including the anion form of the methanethiol, the cation form of the imidazole and the anion form of the formic acid was the most stable of the various hydrogen-bonding structures. This result is in good agreement with experiments on the electronic structure in the active site of papain, and it supports the mechanism of the enzymatic reaction proposed by Angelides and Fink.