1tv5
From Proteopedia
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| - | {{Seed}} | ||
| - | [[Image:1tv5.png|left|200px]] | ||
| - | < | + | ==Plasmodium falciparum dihydroorotate dehydrogenase with a bound inhibitor== |
| - | + | <StructureSection load='1tv5' size='340' side='right'caption='[[1tv5]], [[Resolution|resolution]] 2.40Å' scene=''> | |
| - | You may | + | == Structural highlights == |
| - | + | <table><tr><td colspan='2'>[[1tv5]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TV5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1TV5 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]] 2.4Å</td></tr> | |
| - | -- | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A26:(2Z)-2-CYANO-3-HYDROXY-N-[4-(TRIFLUOROMETHYL)PHENYL]BUT-2-ENAMIDE'>A26</scene>, <scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=N8E:3,6,9,12,15-PENTAOXATRICOSAN-1-OL'>N8E</scene>, <scene name='pdbligand=ORO:OROTIC+ACID'>ORO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=1tv5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tv5 OCA], [https://pdbe.org/1tv5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1tv5 RCSB], [https://www.ebi.ac.uk/pdbsum/1tv5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1tv5 ProSAT]</span></td></tr> | |
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/PYRD_PLAF7 PYRD_PLAF7] 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/tv/1tv5_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=1tv5 ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Membrane-associated dihydroorotate dehydrogenase (DHODH) is an antimalarial therapeutic target without an effective inhibitor. Studies on human DHODH (HsDHODH) led to a structural mechanistic model in which respiratory quinones bind in a tunnel formed by the highly variable N-terminus that leads to the flavin mononucleotide-binding site. The therapeutic agents leflunomide (Arava) and brequinar sodium inhibit HsDHODH by binding in this tunnel. Plasmodium falciparum DHODH (PfDHODH) and HsDHODH have markedly different sensitivities to the two drugs. To understand the structural basis of this differential sensitivity and begin a structure-based drug-design cycle for PfDHODH inhibitors, the three-dimensional structure (2.4 Angstroms, R = 20.1%) of PfDHODH bound to the active metabolite of leflunomide was determined by X-ray crystallography. Comparison of the structures of HsDHODH and PfDHODH reveals a completely different binding mode for the same inhibitor in these two catalytically identical enzymes and explains the previously observed species-specific preferential binding. Because no effective inhibitors have been described for PfDHODH, this structure provides critical insight for the design of potential antimalarials. | ||
| - | + | Structure of Plasmodium falciparum dihydroorotate dehydrogenase with a bound inhibitor.,Hurt DE, Widom J, Clardy J Acta Crystallogr D Biol Crystallogr. 2006 Mar;62(Pt 3):312-23. Epub 2006, Feb 22. PMID:16510978<ref>PMID:16510978</ref> | |
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 1tv5" style="background-color:#fffaf0;"></div> | ||
| - | + | ==See Also== | |
| - | + | *[[Dihydroorotate dehydrogenase 3D structures|Dihydroorotate dehydrogenase 3D structures]] | |
| - | + | == References == | |
| - | + | <references/> | |
| - | + | __TOC__ | |
| - | + | </StructureSection> | |
| - | == | + | [[Category: Large Structures]] |
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| - | == | + | |
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[[Category: Plasmodium falciparum]] | [[Category: Plasmodium falciparum]] | ||
| - | + | [[Category: Clardy J]] | |
| - | [[Category: Clardy | + | [[Category: Hurt DE]] |
| - | [[Category: Hurt | + | [[Category: Widom J]] |
| - | [[Category: Widom | + | |
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Current revision
Plasmodium falciparum dihydroorotate dehydrogenase with a bound inhibitor
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