2wv8

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[[Image:2wv8.png|left|200px]]
 
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==Complex of human dihydroorotate dehydrogenase with the inhibitor 221290==
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The line below this paragraph, containing "STRUCTURE_2wv8", creates the "Structure Box" on the page.
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<StructureSection load='2wv8' size='340' side='right'caption='[[2wv8]], [[Resolution|resolution]] 1.90&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'>[[2wv8]] 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=2WV8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WV8 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=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=DDQ:DECYLAMINE-N,N-DIMETHYL-N-OXIDE'>DDQ</scene>, <scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=ORO:OROTIC+ACID'>ORO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=VGN:2-ACETAMIDO-5-(4-PHENYLPHENYL)BENZOIC+ACID'>VGN</scene></td></tr>
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{{STRUCTURE_2wv8| PDB=2wv8 | 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=2wv8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wv8 OCA], [https://pdbe.org/2wv8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wv8 RCSB], [https://www.ebi.ac.uk/pdbsum/2wv8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wv8 ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/PYRD_HUMAN PYRD_HUMAN] Defects in DHODH are the cause of postaxial acrofacial dysostosis (POADS) [MIM:[https://omim.org/entry/263750 263750]; also known as Miller syndrome. POADS is characterized by severe micrognathia, cleft lip and/or palate, hypoplasia or aplasia of the posterior elements of the limbs, coloboma of the eyelids and supernumerary nipples. POADS is a very rare disorder: only 2 multiplex families, each consisting of 2 affected siblings born to unaffected, nonconsanguineous parents, have been described among a total of around 30 reported cases.<ref>PMID:19915526</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/PYRD_HUMAN PYRD_HUMAN] Catalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor.
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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/wv/2wv8_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=2wv8 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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A strategy that combines virtual screening and structure-guided selection of fragments was used to identify three unexplored classes of human DHODH inhibitor compounds: 4-hydroxycoumarins, fenamic acids, and N-(alkylcarbonyl)anthranilic acids. Structure-guided selection of fragments targeting the inner subsite of the DHODH ubiquinone binding site made these findings possible with screening of fewer than 300 fragments in a DHODH assay. Fragments from the three inhibitor classes identified were subsequently chemically expanded to target an additional subsite of hydrophobic character. All three classes were found to exhibit distinct structure-activity relationships upon expansion. The novel N-(alkylcarbonyl)anthranilic acid class shows the most promising potency against human DHODH, with IC(50) values in the low nanomolar range. The structure of human DHODH in complex with an inhibitor of this class is presented.
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===Complex of human dihydroorotate dehydrogenase with the inhibitor 221290===
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Inhibition of human DHODH by 4-hydroxycoumarins, fenamic acids, and N-(alkylcarbonyl)anthranilic acids identified by structure-guided fragment selection.,Fritzson I, Svensson B, Al-Karadaghi S, Walse B, Wellmar U, Nilsson UJ, da Graca Thrige D, Jonsson S ChemMedChem. 2010 Apr 6;5(4):608-17. PMID:20183850<ref>PMID:20183850</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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</div>
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<div class="pdbe-citations 2wv8" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_20183850}}, adds the Publication Abstract to the page
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*[[Dihydroorotate dehydrogenase 3D structures|Dihydroorotate dehydrogenase 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 20183850 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_20183850}}
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__TOC__
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</StructureSection>
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==About this Structure==
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[[2wv8]] is a 1 chain structure with sequence 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=2WV8 OCA].
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==Reference==
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<ref group="xtra">PMID:020183850</ref><references group="xtra"/>
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[[Category: Dihydroorotate dehydrogenase]]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Al-Karadaghi, S.]]
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[[Category: Large Structures]]
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[[Category: Dahlberg, L.]]
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[[Category: Al-Karadaghi S]]
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[[Category: Fritzson, I.]]
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[[Category: Dahlberg L]]
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[[Category: Svensson, B.]]
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[[Category: Fritzson I]]
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[[Category: Walse, B.]]
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[[Category: Svensson B]]
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[[Category: Wellmar, U.]]
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[[Category: Walse B]]
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[[Category: Enzyme inhibition]]
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[[Category: Wellmar U]]
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[[Category: Flavoprotein]]
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[[Category: Inflamation]]
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[[Category: Mitochondrion inner membrane]]
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[[Category: Oxidoreductase]]
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[[Category: Pyrimidine biosynthesis]]
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[[Category: Structure-based drug design]]
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[[Category: Transit peptide]]
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[[Category: Transmembrane]]
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Current revision

Complex of human dihydroorotate dehydrogenase with the inhibitor 221290

PDB ID 2wv8

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