Sandbox 181
From Proteopedia
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Glutathione reductase, also known as GSH reductase, converts oxidized glutathione (GSSG) to two molecules of reduced [[gluthatione]] (GSH). | Glutathione reductase, also known as GSH reductase, converts oxidized glutathione (GSSG) to two molecules of reduced [[gluthatione]] (GSH). | ||
{{STRUCTURE_3djj| PDB=3djj |SCENE=Sandbox_181/Cpk_default/1}} | {{STRUCTURE_3djj| PDB=3djj |SCENE=Sandbox_181/Cpk_default/1}} | ||
| - | + | =Structure= | |
| - | Glutathione reductase belongs to the larger family of [[flavoezymes]], which use a [[flavin adenine dinucleotide]] (FAD) or [[flavin mononucleotide]] (FMN) in catalysis. It is an | + | Glutathione reductase belongs to the larger family of [[flavoezymes]], which use a [[flavin adenine dinucleotide]] (FAD) or [[flavin mononucleotide]] (FMN) in catalysis. It is an oxiodreductase homodimer of 52kD monomers of which, each has three domains: |
1. NADPH-binding domain, | 1. NADPH-binding domain, | ||
2. FAD-binding domain, | 2. FAD-binding domain, | ||
3. dimerization domain. | 3. dimerization domain. | ||
| - | + | =Reaction= | |
| - | The action of glutathione reductase proceeds through a cyclic series of structures in differing redox states | + | The action of glutathione reductase proceeds through a cyclic series of structures in differing redox states . NADPH binds causing a transient reduction of flavin and this reduced flavin consequently reduces Cys58-Cys63 disulfide bond, forming a short lived covalent intermediate with Cys63. Following this, a stable charge-transfer complex between flavin and the Cys63 thiolate forms. After formation the NADP+ dissociates and is replaced by another NADPH. This is the end of the reductive first half of the mechanism and the oxidative half is initiated upon the binding of GSSG. The Cys58 in glutathione reductase attacks CysI of the GSSG to form a mixed disulfide between the first GS and Cys58. The second GSH is the free to leave and the disulfide bond is reformed between Cys58 and Cys63 of glutathione reductase. Finally, the first molecule of GSH is released. The glutathione reductase is then able to be recycled to allow for the binding of NADPH once again<ref>PMID:18638483</ref>. |
| - | + | =Function= | |
| - | + | ==Mechanism== | |
<scene name='Sandbox_181/Ligands_glutationereductase/1'>Highlighting Ligands</scene> | <scene name='Sandbox_181/Ligands_glutationereductase/1'>Highlighting Ligands</scene> | ||
| - | + | =References= | |
| + | <references/> | ||
Human Glutathione Reductase | Human Glutathione Reductase | ||
<table style="background-color:#ffffc0" cellpadding="8" width="95%" border="0"><tr><td>Please do NOT make changes to this Sandbox until after April 23, 2010. Sandboxes 151-200 are reserved until then for use by the Chemistry 307 class at UNBC taught by Prof. [[User:Andrea Gorrell|Andrea Gorrell]].</td></tr> | <table style="background-color:#ffffc0" cellpadding="8" width="95%" border="0"><tr><td>Please do NOT make changes to this Sandbox until after April 23, 2010. Sandboxes 151-200 are reserved until then for use by the Chemistry 307 class at UNBC taught by Prof. [[User:Andrea Gorrell|Andrea Gorrell]].</td></tr> | ||
Josina Rhebergen | Josina Rhebergen | ||
Revision as of 02:13, 19 March 2010
Glutathione reductase, also known as GSH reductase, converts oxidized glutathione (GSSG) to two molecules of reduced gluthatione (GSH).
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| 3djj, resolution 1.10Å () | |||||||
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| Ligands: | , , , , | ||||||
| Gene: | GSR, GLUR, GRD1 (HUMAN) | ||||||
| Activity: | Glutathione-disulfide reductase, with EC number 1.8.1.7 | ||||||
| Related: | 3djg | ||||||
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| Resources: | FirstGlance, OCA, RCSB, PDBsum | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Contents |
Structure
Glutathione reductase belongs to the larger family of flavoezymes, which use a flavin adenine dinucleotide (FAD) or flavin mononucleotide (FMN) in catalysis. It is an oxiodreductase homodimer of 52kD monomers of which, each has three domains: 1. NADPH-binding domain, 2. FAD-binding domain, 3. dimerization domain.
Reaction
The action of glutathione reductase proceeds through a cyclic series of structures in differing redox states . NADPH binds causing a transient reduction of flavin and this reduced flavin consequently reduces Cys58-Cys63 disulfide bond, forming a short lived covalent intermediate with Cys63. Following this, a stable charge-transfer complex between flavin and the Cys63 thiolate forms. After formation the NADP+ dissociates and is replaced by another NADPH. This is the end of the reductive first half of the mechanism and the oxidative half is initiated upon the binding of GSSG. The Cys58 in glutathione reductase attacks CysI of the GSSG to form a mixed disulfide between the first GS and Cys58. The second GSH is the free to leave and the disulfide bond is reformed between Cys58 and Cys63 of glutathione reductase. Finally, the first molecule of GSH is released. The glutathione reductase is then able to be recycled to allow for the binding of NADPH once again[1].
Function
Mechanism
References
- ↑ Berkholz DS, Faber HR, Savvides SN, Karplus PA. Catalytic cycle of human glutathione reductase near 1 A resolution. J Mol Biol. 2008 Oct 3;382(2):371-84. Epub 2008 Jul 7. PMID:18638483 doi:10.1016/j.jmb.2008.06.083
Human Glutathione Reductase
| Please do NOT make changes to this Sandbox until after April 23, 2010. Sandboxes 151-200 are reserved until then for use by the Chemistry 307 class at UNBC taught by Prof. Andrea Gorrell. |
