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1pl6

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(New page: 200px<br /> <applet load="1pl6" size="450" color="white" frame="true" align="right" spinBox="true" caption="1pl6, resolution 2.00&Aring;" /> '''Human SDH/NADH/inhi...)
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[[Image:1pl6.gif|left|200px]]<br />
 
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<applet load="1pl6" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1pl6, resolution 2.00&Aring;" />
 
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'''Human SDH/NADH/inhibitor complex'''<br />
 
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==Overview==
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==Human SDH/NADH/inhibitor complex==
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Sorbitol dehydrogenase (hSDH) and aldose reductase form the polyol pathway, that interconverts glucose and fructose. Redox changes from overproduction, of the coenzyme NADH by SDH may play a role in diabetes-induced, dysfunction in sensitive tissues, making SDH a therapeutic target for, diabetic complications. We have purified and determined the crystal, structures of human SDH alone, SDH with NAD(+), and SDH with NADH and an, inhibitor that is competitive with fructose. hSDH is a tetramer of, identical, catalytically active subunits. In the apo and NAD(+) complex, the catalytic zinc is coordinated by His69, Cys44, Glu70, and a water, molecule. The inhibitor coordinates the zinc through an oxygen and a, nitrogen atom with the concomitant dissociation of Glu70. The inhibitor, forms hydrophobic interactions to NADH and likely sterically occludes, substrate binding. The structure of the inhibitor complex provides a, framework for developing more potent inhibitors of hSDH.
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<StructureSection load='1pl6' size='340' side='right'caption='[[1pl6]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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== Structural highlights ==
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==Disease==
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<table><tr><td colspan='2'>[[1pl6]] is a 4 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=1PL6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PL6 FirstGlance]. <br>
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Known disease associated with this structure: Cataract, congenital (2) OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=182500 182500]]
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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]] 2&#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=572:4-[2-(HYDROXYMETHYL)PYRIMIDIN-4-YL]-N,N-DIMETHYLPIPERAZINE-1-SULFONAMIDE'>572</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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==About this Structure==
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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=1pl6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pl6 OCA], [https://pdbe.org/1pl6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pl6 RCSB], [https://www.ebi.ac.uk/pdbsum/1pl6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pl6 ProSAT]</span></td></tr>
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1PL6 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 ZN, NAD and 572 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/L-iditol_2-dehydrogenase L-iditol 2-dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.14 1.1.1.14] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1PL6 OCA].
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</table>
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== Function ==
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==Reference==
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[https://www.uniprot.org/uniprot/DHSO_HUMAN DHSO_HUMAN] Converts sorbitol to fructose. Part of the polyol pathway that plays an important role in sperm physiology. May play a role in the sperm motility by providing an energetic source for sperm (By similarity).<ref>PMID:16278369</ref>
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X-ray crystallographic and kinetic studies of human sorbitol dehydrogenase., Pauly TA, Ekstrom JL, Beebe DA, Chrunyk B, Cunningham D, Griffor M, Kamath A, Lee SE, Madura R, Mcguire D, Subashi T, Wasilko D, Watts P, Mylari BL, Oates PJ, Adams PD, Rath VL, Structure. 2003 Sep;11(9):1071-85. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12962626 12962626]
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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/pl/1pl6_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=1pl6 ConSurf].
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<div style="clear:both"></div>
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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: L-iditol 2-dehydrogenase]]
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[[Category: Large Structures]]
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[[Category: Single protein]]
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[[Category: Adams PD]]
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[[Category: Adams, P.D.]]
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[[Category: Beebe DA]]
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[[Category: Beebe, D.A.]]
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[[Category: Chrunyk B]]
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[[Category: Chrunyk, B.]]
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[[Category: Cunningham D]]
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[[Category: Cunningham, D.]]
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[[Category: Ekstrom JL]]
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[[Category: Ekstrom, J.L.]]
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[[Category: Griffor M]]
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[[Category: Griffor, M.]]
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[[Category: Kamath A]]
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[[Category: Kamath, A.]]
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[[Category: Lee SE]]
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[[Category: Lee, S.E.]]
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[[Category: Madura R]]
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[[Category: Madura, R.]]
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[[Category: Mcguire D]]
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[[Category: Mcguire, D.]]
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[[Category: Mylari BL]]
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[[Category: Mylari, B.L.]]
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[[Category: Oates PJ]]
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[[Category: Oates, P.J.]]
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[[Category: Pauly TA]]
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[[Category: Pauly, T.A.]]
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[[Category: Rath VL]]
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[[Category: Rath, V.L.]]
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[[Category: Subashi T]]
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[[Category: Subashi, T.]]
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[[Category: Wasilko D]]
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[[Category: Wasilko, D.]]
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[[Category: Watts P]]
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[[Category: Watts, P.]]
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[[Category: 572]]
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[[Category: NAD]]
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[[Category: ZN]]
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[[Category: 572]]
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[[Category: cp-166]]
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[[Category: sorbitol dehydrogenase]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 18:44:41 2007''
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Current revision

Human SDH/NADH/inhibitor complex

PDB ID 1pl6

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