3grt

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[[Image:3grt.jpg|left|200px]]<br /><applet load="3grt" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:3grt.jpg|left|200px]]
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caption="3grt, resolution 2.50&Aring;" />
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'''HUMAN GLUTATHIONE REDUCTASE A34E, R37W MUTANT, OXIDIZED TRYPANOTHIONE COMPLEX'''<br />
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{{Structure
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|PDB= 3grt |SIZE=350|CAPTION= <scene name='initialview01'>3grt</scene>, resolution 2.50&Aring;
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|SITE= <scene name='pdbsite=S1:The+Active+Site+HIS+(HIS+467)+Is+From+The+Other+Subunit'>S1</scene>
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|LIGAND= <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene> and <scene name='pdbligand=TS2:2-AMINO-4-[4-(4-AMINO-4-CARBOXY-BUTYRYLAMINO)-5,8,19,22-TETRAOXO-1,2-DITHIA-6,9,13,18,21-PENTAAZA-CYCLOTETRACOS-23-YLCARBAMOYL]-BUTYRIC ACID'>TS2</scene>
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|ACTIVITY= [http://en.wikipedia.org/wiki/Transferred_entry:_1.8.1.7 Transferred entry: 1.8.1.7], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.6.4.2 1.6.4.2]
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|GENE=
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}}
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'''HUMAN GLUTATHIONE REDUCTASE A34E, R37W MUTANT, OXIDIZED TRYPANOTHIONE COMPLEX'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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3GRT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=FAD:'>FAD</scene> and <scene name='pdbligand=TS2:'>TS2</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Transferred_entry:_1.8.1.7 Transferred entry: 1.8.1.7], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.6.4.2 1.6.4.2] Known structural/functional Site: <scene name='pdbsite=S1:The+Active+Site+HIS+(HIS+467)+Is+From+The+Other+Subunit'>S1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GRT OCA].
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3GRT is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GRT OCA].
==Reference==
==Reference==
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=2059620 2059620]
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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:[http://www.ncbi.nlm.nih.gov/pubmed/2059620 2059620]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: oxidoreductase]]
[[Category: oxidoreductase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 19:09:36 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 19:05:03 2008''

Revision as of 17:05, 20 March 2008


PDB ID 3grt

Drag the structure with the mouse to rotate
, resolution 2.50Å
Sites:
Ligands: and
Activity: Transferred entry: 1.8.1.7, with EC number 1.6.4.2
Coordinates: save as pdb, mmCIF, xml



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. 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

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