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2b0m
From Proteopedia
(Difference between revisions)
(New page: 200px<br /> <applet load="2b0m" size="450" color="white" frame="true" align="right" spinBox="true" caption="2b0m, resolution 2.00Å" /> '''Human dihydroorotat...) |
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| - | [[Image:2b0m.gif|left|200px]]<br /> | ||
| - | <applet load="2b0m" size="450" color="white" frame="true" align="right" spinBox="true" | ||
| - | caption="2b0m, resolution 2.00Å" /> | ||
| - | '''Human dihydroorotate dehydrogenase bound to a novel inhibitor'''<br /> | ||
| - | == | + | ==Human dihydroorotate dehydrogenase bound to a novel inhibitor== |
| - | + | <StructureSection load='2b0m' size='340' side='right'caption='[[2b0m]], [[Resolution|resolution]] 2.00Å' scene=''> | |
| - | + | == Structural highlights == | |
| - | + | <table><tr><td colspan='2'>[[2b0m]] 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=2B0M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2B0M 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]] 2Å</td></tr> | |
| - | [ | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=201:3-AMIDO-5-BIPHENYL-BENZOIC+ACID'>201</scene>, <scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=ORO:OROTIC+ACID'>ORO</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=2b0m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2b0m OCA], [https://pdbe.org/2b0m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2b0m RCSB], [https://www.ebi.ac.uk/pdbsum/2b0m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2b0m ProSAT]</span></td></tr> |
| - | [ | + | </table> |
| - | [[ | + | == Disease == |
| - | [ | + | [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> |
| - | [[ | + | == Function == |
| - | [ | + | [https://www.uniprot.org/uniprot/PYRD_HUMAN PYRD_HUMAN] Catalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor. |
| + | == 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/b0/2b0m_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=2b0m ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Therapeutic agents brequinar sodium and leflunomide (Arava) work by binding in a hydrophobic tunnel formed by a highly variable N-terminus of family 2 dihydroorotate dehydrogenase (DHODH). The X-ray crystallographic structure of an analog of brequinar bound to human DHODH was determined. In silico screening of a library of compounds suggested another subset of brequinar analogs that do not inhibit human DHODH as potentially effective inhibitors of Plasmodium falciparum DHODH. | ||
| - | + | Brequinar derivatives and species-specific drug design for dihydroorotate dehydrogenase.,Hurt DE, Sutton AE, Clardy J Bioorg Med Chem Lett. 2006 Mar 15;16(6):1610-5. Epub 2006 Jan 10. PMID:16406782<ref>PMID:16406782</ref> | |
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 2b0m" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Dihydroorotate dehydrogenase|Dihydroorotate dehydrogenase]] | ||
| + | *[[Dihydroorotate dehydrogenase 3D structures|Dihydroorotate dehydrogenase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Clardy J]] | ||
| + | [[Category: Hurt DE]] | ||
| + | [[Category: Sutton AE]] | ||
Current revision
Human dihydroorotate dehydrogenase bound to a novel inhibitor
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