3grt
From Proteopedia
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HUMAN GLUTATHIONE REDUCTASE A34E, R37W MUTANT, OXIDIZED TRYPANOTHIONE COMPLEX
Contents |
Overview
The substrate specificity of the human enzyme glutathione reductase was, changed from its natural substrate glutathione to trypanothione, [N1,N8-bis(glutathionyl)spermidine] by site-directed mutagenesis of two, residues. The glutathione analogue, trypanothione, is the natural, substrate for trypanothione reductase, an enzyme found in trypanosomatids, and leishmanias, the causative agents of diseases such as African sleeping, sickness, Chagas disease, and Oriental sore. The rational bases for our, mutational experiments were the availability of a high-resolution X-ray, structure for human glutathione reductase with bound substrates, the, active site sequence comparisons of human glutathione reductase and the, trypanothione reductases from Trypanosoma congolense and Trypanosoma, cruzi, a complementary set of mutants in T. congolense trypanothione, reductase, and the properties of substrate analogues of trypanothione., Mutation of two residues, A34----E34 and R37----W37, in the, glutathione-binding site of human glutathione reductase switches human, glutathione reductase into a trypanothione reductase with a preference for, trypanothione over glutathione by a factor of 700 using kcat/Km as a, criterion.
Disease
Known diseases associated with this structure: Hemolytic anemia due to glutathione reductase deficiency OMIM:[138300], Mental retardation, autosomal recessive, 6 OMIM:[138244]
About this Structure
3GRT is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as Transferred entry: 1.8.1.7, with EC number 1.6.4.2 Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
Redox enzyme engineering: conversion of human glutathione reductase into a trypanothione reductase., Bradley M, Bucheler US, Walsh CT, Biochemistry. 1991 Jun 25;30(25):6124-7. PMID:2059620
Page seeded by OCA on Sun Feb 3 10:51:55 2008
