1gsn
From Proteopedia
(New page: 200px<br /> <applet load="1gsn" size="450" color="white" frame="true" align="right" spinBox="true" caption="1gsn, resolution 1.7Å" /> '''HUMAN GLUTATHIONE RE...) |
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| - | [[Image:1gsn.gif|left|200px]]<br /> | + | [[Image:1gsn.gif|left|200px]]<br /><applet load="1gsn" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1gsn" size=" | + | |
caption="1gsn, resolution 1.7Å" /> | caption="1gsn, resolution 1.7Å" /> | ||
'''HUMAN GLUTATHIONE REDUCTASE MODIFIED BY DINITROSOGLUTATHIONE'''<br /> | '''HUMAN GLUTATHIONE REDUCTASE MODIFIED BY DINITROSOGLUTATHIONE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Nitric oxide (NO) is a pluripotent regulatory molecule, yet the molecular | + | Nitric oxide (NO) is a pluripotent regulatory molecule, yet the molecular mechanisms by which it exerts its effects are largely unknown. Few physiologic target molecules of NO have been identified, and even for these, the modifications caused by NO remain uncharacterized. Human glutathione reductase (hGR), a central enzyme of cellular antioxidant defense, is inhibited by S-nitrosoglutathione (GSNO) and by diglutathionyl-dinitroso-iron (DNIC-[GSH]2), two in vivo transport forms of NO. Here, crystal structures of hGR inactivated by GSNO and DNIC-[GSH]2 at 1.7 A resolution provide the first picture of enzyme inactivation by NO-carriers: in GSNO-modified hGR, the active site residue Cys 63 is oxidized to an unusually stable cysteine sulfenic acid (R-SOH), whereas modification with DNIC-[GSH]2 oxidizes Cys 63 to a cysteine sulfinic acid (R-SO2H). Our results illustrate that various forms of NO can mediate distinct chemistry, and that sulfhydryl oxidation must be considered as a major mechanism of NO action. |
==Disease== | ==Disease== | ||
| - | Known | + | 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== | ||
| - | 1GSN 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 PO4, FAD and GTT as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http:// | + | 1GSN 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=PO4:'>PO4</scene>, <scene name='pdbligand=FAD:'>FAD</scene> and <scene name='pdbligand=GTT:'>GTT</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GSN OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Becker, K.]] | [[Category: Becker, K.]] | ||
| - | [[Category: Karplus, P | + | [[Category: Karplus, P A.]] |
[[Category: Keese, M.]] | [[Category: Keese, M.]] | ||
| - | [[Category: Savvides, S | + | [[Category: Savvides, S N.]] |
| - | [[Category: Schirmer, R | + | [[Category: Schirmer, R H.]] |
[[Category: FAD]] | [[Category: FAD]] | ||
[[Category: GTT]] | [[Category: GTT]] | ||
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[[Category: sulfhydryl oxidation]] | [[Category: sulfhydryl oxidation]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:53:29 2008'' |
Revision as of 10:53, 21 February 2008
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HUMAN GLUTATHIONE REDUCTASE MODIFIED BY DINITROSOGLUTATHIONE
Contents |
Overview
Nitric oxide (NO) is a pluripotent regulatory molecule, yet the molecular mechanisms by which it exerts its effects are largely unknown. Few physiologic target molecules of NO have been identified, and even for these, the modifications caused by NO remain uncharacterized. Human glutathione reductase (hGR), a central enzyme of cellular antioxidant defense, is inhibited by S-nitrosoglutathione (GSNO) and by diglutathionyl-dinitroso-iron (DNIC-[GSH]2), two in vivo transport forms of NO. Here, crystal structures of hGR inactivated by GSNO and DNIC-[GSH]2 at 1.7 A resolution provide the first picture of enzyme inactivation by NO-carriers: in GSNO-modified hGR, the active site residue Cys 63 is oxidized to an unusually stable cysteine sulfenic acid (R-SOH), whereas modification with DNIC-[GSH]2 oxidizes Cys 63 to a cysteine sulfinic acid (R-SO2H). Our results illustrate that various forms of NO can mediate distinct chemistry, and that sulfhydryl oxidation must be considered as a major mechanism of NO action.
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
1GSN is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as Glutathione-disulfide reductase, with EC number 1.8.1.7 Full crystallographic information is available from OCA.
Reference
Enzyme inactivation through sulfhydryl oxidation by physiologic NO-carriers., Becker K, Savvides SN, Keese M, Schirmer RH, Karplus PA, Nat Struct Biol. 1998 Apr;5(4):267-71. PMID:9546215
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