View source for 1pl6


==Human SDH/NADH/inhibitor complex==
<StructureSection load='1pl6' size='340' side='right'caption='[[1pl6]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<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>
</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>
<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>
<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>
</table>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pl/1pl6_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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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== Publication Abstract from PubMed ==
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.

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:12962626<ref>PMID:12962626</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1pl6" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Adams PD]]
[[Category: Beebe DA]]
[[Category: Chrunyk B]]
[[Category: Cunningham D]]
[[Category: Ekstrom JL]]
[[Category: Griffor M]]
[[Category: Kamath A]]
[[Category: Lee SE]]
[[Category: Madura R]]
[[Category: Mcguire D]]
[[Category: Mylari BL]]
[[Category: Oates PJ]]
[[Category: Pauly TA]]
[[Category: Rath VL]]
[[Category: Subashi T]]
[[Category: Wasilko D]]
[[Category: Watts P]]