2qg4

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{{Seed}}
 
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[[Image:2qg4.png|left|200px]]
 
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==Crystal structure of human UDP-glucose dehydrogenase product complex with UDP-glucuronate==
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The line below this paragraph, containing "STRUCTURE_2qg4", creates the "Structure Box" on the page.
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<StructureSection load='2qg4' size='340' side='right'caption='[[2qg4]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2qg4]] is a 8 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=2QG4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QG4 FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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]] 2.1&#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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=UGA:URIDINE-5-DIPHOSPHATE-GLUCURONIC+ACID'>UGA</scene></td></tr>
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{{STRUCTURE_2qg4| PDB=2qg4 | SCENE= }}
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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=2qg4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qg4 OCA], [https://pdbe.org/2qg4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qg4 RCSB], [https://www.ebi.ac.uk/pdbsum/2qg4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qg4 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/UGDH_HUMAN UGDH_HUMAN] Involved in the biosynthesis of glycosaminoglycans; hyaluronan, chondroitin sulfate, and heparan sulfate.
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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/qg/2qg4_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=2qg4 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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Elevated production of the matrix glycosaminoglycan hyaluronan is strongly implicated in epithelial tumor progression. Inhibition of synthesis of the hyaluronan precursor UDP-glucuronic acid (UDP-GlcUA) therefore presents an emerging target for cancer therapy. Human UDP-glucose 6-dehydrogenase (hUGDH) catalyzes, in two NAD(+)-dependent steps without release of intermediate aldehyde, the biosynthetic oxidation of UDP-glucose (UDP-Glc) to UDP-GlcUA. Here, we present a structural characterization of the hUGDH reaction coordinate using crystal structures of the apoenzyme and ternary complexes of the enzyme bound with UDP-Glc/NADH and UDP-GlcUA/NAD(+). The quaternary structure of hUGDH is a disc-shaped trimer of homodimers whose subunits consist of two discrete alpha/beta domains with the active site located in the interdomain cleft. Ternary complex formation is accompanied by rigid-body and restrained movement of the N-terminal NAD(+) binding domain, sequestering substrate and coenzyme in their reactive positions through interdomain closure. By alternating between conformations in and out of the active site during domain motion, Tyr(14), Glu(161), and Glu(165) participate in control of coenzyme binding and release during 2-fold oxidation. The proposed mechanism of hUGDH involves formation and breakdown of thiohemiacetal and thioester intermediates whereby Cys(276) functions as the catalytic nucleophile. Stopped-flow kinetic data capture the essential deprotonation of Cys(276) in the course of the first oxidation step, allowing the thiolate side chain to act as a trap of the incipient aldehyde. Because thiohemiacetal intermediate accumulates at steady state under physiological reaction conditions, hUGDH inhibition might best explore ligand binding to the NAD(+) binding domain.
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===Crystal structure of human UDP-glucose dehydrogenase product complex with UDP-glucuronate===
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Structure and mechanism of human UDP-glucose 6-dehydrogenase.,Egger S, Chaikuad A, Kavanagh KL, Oppermann U, Nidetzky B J Biol Chem. 2011 Jul 8;286(27):23877-87. Epub 2011 Apr 18. PMID:21502315<ref>PMID:21502315</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==About this Structure==
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</div>
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2QG4 is a 8 chains structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QG4 OCA].
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<div class="pdbe-citations 2qg4" style="background-color:#fffaf0;"></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: UDP-glucose 6-dehydrogenase]]
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[[Category: Large Structures]]
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[[Category: Arrowsmith, C H.]]
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[[Category: Arrowsmith CH]]
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[[Category: Berridge, G.]]
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[[Category: Berridge G]]
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[[Category: Bhatia, C.]]
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[[Category: Bhatia C]]
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[[Category: Bunkoczi, G.]]
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[[Category: Bunkoczi G]]
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[[Category: Delft, F von.]]
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[[Category: Edwards A]]
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[[Category: Edwards, A.]]
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[[Category: Guo K]]
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[[Category: Guo, K.]]
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[[Category: Kavanagh KL]]
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[[Category: Kavanagh, K L.]]
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[[Category: Niesen F]]
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[[Category: Niesen, F.]]
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[[Category: Oppermann U]]
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[[Category: Oppermann, U.]]
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[[Category: Pilka E]]
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[[Category: Pilka, E.]]
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[[Category: Savitsky P]]
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[[Category: SGC, Structural Genomics Consortium.]]
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[[Category: Smee C]]
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[[Category: Savitsky, P.]]
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[[Category: Sundstrom M]]
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[[Category: Smee, C.]]
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[[Category: Weigelt J]]
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[[Category: Sundstrom, M.]]
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[[Category: Von Delft F]]
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[[Category: Weigelt, J.]]
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[[Category: Hexamer]]
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[[Category: Oxidoreductase]]
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[[Category: Sgc]]
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[[Category: Structural genomic]]
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[[Category: Structural genomics consortium]]
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[[Category: Udp-glucose 6-dehydrogenase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Nov 11 22:44:15 2009''
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Current revision

Crystal structure of human UDP-glucose dehydrogenase product complex with UDP-glucuronate

PDB ID 2qg4

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