3grt
From Proteopedia
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'''HUMAN GLUTATHIONE REDUCTASE A34E, R37W MUTANT, OXIDIZED TRYPANOTHIONE COMPLEX''' | '''HUMAN GLUTATHIONE REDUCTASE A34E, R37W MUTANT, OXIDIZED TRYPANOTHIONE COMPLEX''' | ||
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[[Category: Stoll, V S.]] | [[Category: Stoll, V S.]] | ||
[[Category: Walsh, C T.]] | [[Category: Walsh, C T.]] | ||
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| - | [[Category: | + | [[Category: Mixed disulfide]] |
| - | [[Category: | + | [[Category: Oxidoreductase]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 22:03:04 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 19:03, 4 May 2008
HUMAN GLUTATHIONE REDUCTASE A34E, R37W MUTANT, OXIDIZED TRYPANOTHIONE COMPLEX
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.
About this Structure
3GRT is a Single protein structure of sequence from Homo sapiens. 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 May 4 22:03:04 2008
