3f1q

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[[Image:3f1q.png|left|200px]]
 
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{{STRUCTURE_3f1q| PDB=3f1q | SCENE= }}
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==Human dihydroorotate dehydrogenase in complex with a leflunomide derivative inhibitor 1==
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<StructureSection load='3f1q' size='340' side='right'caption='[[3f1q]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3f1q]] 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=3F1Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3F1Q 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]] 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=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=BCE:(2Z)-N-BIPHENYL-4-YL-2-CYANO-3-HYDROXYBUT-2-ENAMIDE'>BCE</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></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=3f1q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f1q OCA], [https://pdbe.org/3f1q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3f1q RCSB], [https://www.ebi.ac.uk/pdbsum/3f1q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3f1q 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/f1/3f1q_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=3f1q 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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Pyrimidine biosynthesis is an attractive drug target in a variety of organisms, including humans and the malaria parasite Plasmodium falciparum. Dihydroorotate dehydrogenase, an enzyme catalyzing the only redox reaction of the pyrimidine biosynthesis pathway, is a well-characterized target for chemotherapeutical intervention. In this study, we have applied SPROUT-LeadOpt, a software package for structure-based drug discovery and lead optimization, to improve the binding of the active metabolite of the anti-inflammatory drug leflunomide to the target cavities of the P. falciparum and human dihydroorotate dehydrogenases. Following synthesis of a library of compounds based upon the SPROUT-optimized molecular scaffolds, a series of inhibitors generally showing good inhibitory activity was obtained, in keeping with the SPROUT-LeadOpt predictions. Furthermore, cocrystal structures of five of these SPROUT-designed inhibitors bound in the ubiquinone binding cavity of the human dihydroorotate dehydrogenase are also analyzed.
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===Human dihydroorotate dehydrogenase in complex with a leflunomide derivative inhibitor 1===
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Structure-based design, synthesis, and characterization of inhibitors of human and Plasmodium falciparum dihydroorotate dehydrogenases.,Davies M, Heikkila T, McConkey GA, Fishwick CW, Parsons MR, Johnson AP J Med Chem. 2009 May 14;52(9):2683-93. PMID:19351152<ref>PMID:19351152</ref>
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{{ABSTRACT_PUBMED_19351152}}
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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 3f1q" style="background-color:#fffaf0;"></div>
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==About this Structure==
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==See Also==
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[[3f1q]] 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=3F1Q OCA].
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*[[Dihydroorotate dehydrogenase 3D structures|Dihydroorotate dehydrogenase 3D structures]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:019351152</ref><references group="xtra"/>
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__TOC__
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[[Category: Dihydroorotate oxidase]]
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Davies, M.]]
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[[Category: Large Structures]]
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[[Category: Fishwick, C W.G.]]
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[[Category: Davies M]]
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[[Category: Heikkila, T.]]
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[[Category: Fishwick CWG]]
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[[Category: Johnson, A P.]]
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[[Category: Heikkila T]]
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[[Category: McConkey, G A.]]
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[[Category: Johnson AP]]
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[[Category: Parsons, M R.]]
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[[Category: McConkey GA]]
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[[Category: Dihydroorotate dehydrogenase]]
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[[Category: Parsons MR]]
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[[Category: Fad]]
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[[Category: Flavoprotein]]
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[[Category: Leflunomide]]
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[[Category: Membrane]]
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[[Category: Mitochondrion]]
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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: Transit peptide]]
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Current revision

Human dihydroorotate dehydrogenase in complex with a leflunomide derivative inhibitor 1

PDB ID 3f1q

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