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

Zheng, Y J; Bruice, T C · Proc Natl Acad Sci U S A · 1997

basic_science · Level V

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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 x 10(5).

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