3grt
From Proteopedia
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|PDB= 3grt |SIZE=350|CAPTION= <scene name='initialview01'>3grt</scene>, resolution 2.50Å | |PDB= 3grt |SIZE=350|CAPTION= <scene name='initialview01'>3grt</scene>, resolution 2.50Å | ||
|SITE= <scene name='pdbsite=S1:The+Active+Site+HIS+(HIS+467)+Is+From+The+Other+Subunit'>S1</scene> | |SITE= <scene name='pdbsite=S1:The+Active+Site+HIS+(HIS+467)+Is+From+The+Other+Subunit'>S1</scene> | ||
| - | |LIGAND= <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene> | + | |LIGAND= <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <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> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/ | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Glutathione-disulfide_reductase Glutathione-disulfide reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.8.1.7 1.8.1.7] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3grt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3grt OCA], [http://www.ebi.ac.uk/pdbsum/3grt PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=3grt RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==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. | 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:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=138300 138300]], Mental retardation, autosomal recessive, 6 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=138244 138244]] | ||
==About this Structure== | ==About this Structure== | ||
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==Reference== | ==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:[http://www.ncbi.nlm.nih.gov/pubmed/2059620 2059620] | 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: Glutathione-disulfide reductase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Transferred entry: 1 8.1 7]] | ||
[[Category: Krauth-Siegel, R L.]] | [[Category: Krauth-Siegel, R L.]] | ||
[[Category: Pai, E F.]] | [[Category: Pai, E F.]] | ||
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[[Category: Stoll, V S.]] | [[Category: Stoll, V S.]] | ||
[[Category: Walsh, C T.]] | [[Category: Walsh, C T.]] | ||
| - | [[Category: FAD]] | ||
| - | [[Category: TS2]] | ||
[[Category: flavoenzyme]] | [[Category: flavoenzyme]] | ||
[[Category: mixed disulfide]] | [[Category: mixed disulfide]] | ||
[[Category: oxidoreductase]] | [[Category: oxidoreductase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 05:33:40 2008'' |
Revision as of 02:33, 31 March 2008
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| , resolution 2.50Å | |||||||
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| Sites: | |||||||
| Ligands: | , | ||||||
| Activity: | Glutathione-disulfide reductase, with EC number 1.8.1.7 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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 Mon Mar 31 05:33:40 2008
