1k4q

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[[Image:1k4q.jpg|left|200px]]<br /><applet load="1k4q" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1k4q, resolution 1.9&Aring;" />
 
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'''Human Glutathione Reductase Inactivated by Peroxynitrite'''<br />
 
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==Overview==
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==Human Glutathione Reductase Inactivated by Peroxynitrite==
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As part of our studies on the nitric oxide-related pathology of cerebral, malaria, we show that the antioxidative enzyme glutathione reductase (GR), is inactivated by peroxynitrite, with GR from the malarial parasite, Plasmodium falciparum being more sensitive than human GR. The crystal, structure of modified human GR at 1.9-A resolution provides the first, picture of protein inactivation by peroxynitrite and reveals that this is, due to the exclusive nitration of 2 Tyr residues (residues 106 and 114) at, the glutathione disulfide-binding site. The selective nitration explains, the impairment of binding the peptide substrate and thus the nearly, 1000-fold decrease in catalytic efficiency (k(cat)/K(m)) of glutathione, reductase observed at physiologic pH. By oxidizing the catalytic dithiol, to a disulfide, peroxynitrite itself can act as a substrate of unmodified, and bisnitrated P. falciparum glutathione reductase.
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<StructureSection load='1k4q' size='340' side='right'caption='[[1k4q]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1k4q]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1K4Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1K4Q FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=NIY:META-NITRO-TYROSINE'>NIY</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1k4q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1k4q OCA], [https://pdbe.org/1k4q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1k4q RCSB], [https://www.ebi.ac.uk/pdbsum/1k4q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1k4q ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/GSHR_HUMAN GSHR_HUMAN] Maintains high levels of reduced glutathione in the cytosol.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/k4/1k4q_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1k4q ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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As part of our studies on the nitric oxide-related pathology of cerebral malaria, we show that the antioxidative enzyme glutathione reductase (GR) is inactivated by peroxynitrite, with GR from the malarial parasite Plasmodium falciparum being more sensitive than human GR. The crystal structure of modified human GR at 1.9-A resolution provides the first picture of protein inactivation by peroxynitrite and reveals that this is due to the exclusive nitration of 2 Tyr residues (residues 106 and 114) at the glutathione disulfide-binding site. The selective nitration explains the impairment of binding the peptide substrate and thus the nearly 1000-fold decrease in catalytic efficiency (k(cat)/K(m)) of glutathione reductase observed at physiologic pH. By oxidizing the catalytic dithiol to a disulfide, peroxynitrite itself can act as a substrate of unmodified and bisnitrated P. falciparum glutathione reductase.
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==Disease==
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Crystal structure of the antioxidant enzyme glutathione reductase inactivated by peroxynitrite.,Savvides SN, Scheiwein M, Bohme CC, Arteel GE, Karplus PA, Becker K, Schirmer RH J Biol Chem. 2002 Jan 25;277(4):2779-84. Epub 2001 Nov 8. PMID:11705998<ref>PMID:11705998</ref>
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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]]
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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1K4Q 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> as [http://en.wikipedia.org/wiki/ligand ligand]. 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=1K4Q OCA].
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</div>
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<div class="pdbe-citations 1k4q" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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Crystal structure of the antioxidant enzyme glutathione reductase inactivated by peroxynitrite., Savvides SN, Scheiwein M, Bohme CC, Arteel GE, Karplus PA, Becker K, Schirmer RH, J Biol Chem. 2002 Jan 25;277(4):2779-84. Epub 2001 Nov 8. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11705998 11705998]
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*[[Glutathione Reductase|Glutathione Reductase]]
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[[Category: Glutathione-disulfide reductase]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Arteel, G.E.]]
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[[Category: Arteel GE]]
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[[Category: Becker, K.]]
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[[Category: Becker K]]
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[[Category: Boehme, C.C.]]
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[[Category: Boehme CC]]
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[[Category: Karplus, P.A.]]
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[[Category: Karplus PA]]
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[[Category: Savvides, S.N.]]
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[[Category: Savvides SN]]
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[[Category: Scheiwein, M.]]
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[[Category: Scheiwein M]]
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[[Category: Schirmer, R.H.]]
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[[Category: Schirmer RH]]
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[[Category: FAD]]
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[[Category: flavoenzyme]]
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[[Category: nitrotyrosine]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:11:24 2008''
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Current revision

Human Glutathione Reductase Inactivated by Peroxynitrite

PDB ID 1k4q

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