Is strong hydrogen bonding in the transition state enough to account for the observed rate acceleration in a mutant of papain?

Is strong hydrogen bonding in the transition state enough to account for the observed rate acceleration in a mutant of papain?

Ya-Jun Zheng and
Thomas C. Bruice†

Department of Chemistry, University of California, Santa Barbara, CA 93106

Abstract

Nitriles are good inhibitors for the cysteine protease papain. However, a single amino acid mutation (Gln-19 → Glu-19) in the active site makes the mutant enzyme a good catalyst for nitrile hydrolysis. A theoretical approach was used to examine the differential transition state stabilization in the papain mutant relative to the wild-type enzyme. Based on this study, we concluded that strong hydrogen bonding in the transition state is responsible for the observed rate enhancement of 4 × 10⁵.