1usb

From Proteopedia

Revision as of 11:51, 30 October 2007

RATIONAL DESIGN OF A NOVEL ENZYME- EFFICIENT THIOESTER HYDROLYSIS ENABLED BY THE INCORPORATION OF A SINGLE HIS RESIDUE INTO HUMAN GLUTATHIONE TRANSFERASE A1-1

Overview

A strategy for rational enzyme design is reported and illustrated by the, engineering of a protein catalyst for thiol-ester hydrolysis. Five mutants, of human glutathione (GSH; gamma-Glu-Cys-Gly) transferase A1-1 were, designed in the search for a catalyst and to provide a set of proteins, from which the reaction mechanism could be elucidated. The single mutant, A216H catalyzed the hydrolysis of the S-benzoyl ester of GSH under, turnover conditions with a k(cat)/K(M) of 156 M(-1) x min(-1), and a, catalytic proficiency of >10(7) M(-1) when compared with the first-order, rate constant of the uncatalyzed reaction. The wild-type enzyme did not, hydrolyze the substrate, and thus, the introduction of a single histidine, residue transformed the wild-type enzyme into a turnover system for, ... [(full description)]

About this Structure

1USB is a [Single protein] structure of sequence from [Homo sapiens] with CL, K and GSH as [ligands]. Active as [Glutathione transferase], with EC number [2.5.1.18]. Structure known Active Site: AC1. Full crystallographic information is available from [OCA].

Reference

Incorporation of a single His residue by rational design enables thiol-ester hydrolysis by human glutathione transferase A1-1., Hederos S, Broo KS, Jakobsson E, Kleywegt GJ, Mannervik B, Baltzer L, Proc Natl Acad Sci U S A. 2004 Sep 7;101(36):13163-7. Epub 2004 Aug 27. PMID:15333749

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