Dihydroorotate dehydrogenase

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== Relevance ==
== Relevance ==
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Leflunomide and brequinar are anti-rheumatic drugs which bind to DHOD.
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Leflunomide and brequinar are anti-rheumatic drugs which bind to DHOD<ref>PMID:19174558</ref>.
== Structural highlights ==
== Structural highlights ==
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<scene name='54/540163/Cv/8'>DHOD FMN/orotate binding site</scene>. The <scene name='54/540163/Cv/9'>inhibitor brequinar binds DHOD in the quinone binding channel</scene>. See also this <scene name='54/540163/Cv/10'>representation of brequinar binding</scene>. <ref>PMID:16406782</ref>
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<scene name='54/540163/Cv/8'>DHOD FMN/orotate binding site</scene>. The <scene name='54/540163/Cv/9'>inhibitor brequinar binds DHOD in the quinone binding channel</scene>. See also this <scene name='54/540163/Cv/11'>representation of brequinar binding</scene>. <ref>PMID:16406782</ref>
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</StructureSection>
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== 3D Structures of dihydroorotate dehydrogenase ==
== 3D Structures of dihydroorotate dehydrogenase ==
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[[Dihydroorotate dehydrogenase 3D structures]]
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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</StructureSection>
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{{#tree:id=OrganizedByTopic|openlevels=0|
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*Dihydroorotate dehydrogenase
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**[[1dor]], [[1jue]] – LlDHOD A – ''Lactococcus lactis''<br />
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**[[1jub]] – LlDHOD A (mutant) <br />
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**[[1ep1]], [[1ep3]] – LlDHOD B<br />
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**[[5ksw]] – LlDHOD A+B (mutant)<br />
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**[[2djx]], [[3c3n]] – TcDHOD – ''Trypanosoma cruzi''<br />
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**[[3tjx]], [[3tro]] – LmDHOD (mutant) – ''Leishmania major''<br />
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**[[4wzh]] – DHOD – ''Leishmania braziliensis''<br />
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**[[4zq6]] – DHOD – ''Mycobacterium tuberculosis''<br />
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**[[4ylf]], [[4yry]] – DHOD A+B – ''Thermotoga maritima''<br />
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*DHOD binary complex
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**[[2dor]] - LlDHOD A + orotate <br />
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**[[1jqv]], [[1jqx]], [[1jrb]], [[1jrc]], [[1ovd]] – LlDHOD A (mutant) + orotate <br />
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**[[2bsl]], [[2bx7]] – LlDHOD A + pyrimidine analog <br />
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**[[1ep2]], [[1ue9]] – LlDHOD B+ orotate <br />
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**[[2djl]] – TcDHOD + succinate <br />
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**[[2e6a]] - TcDHOD + orotate derivative<br />
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**[[2e6d]] – TcDHOD + fumarate <br />
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**[[2e6f]] – TcDHOD + oxonate <br />
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**[[3kvj]], [[3kvk]], [[3kvl]], [[3kvm]] – hDHOD + inhibitor - human<br />
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**[[2bxv]] – hDHOD + orotate<br />
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**[[2e68]] – hDHOD + dihydroorotate<br />
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**[[2b4g]] – TbDHOD + orotate – ''Trypanosoma brucei''<br />
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**[[3c61]] – DHOD + orotate – ''Leishmania donovani''<br />
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**[[3mhu]], [[3mjy]] – LmDHOD + orotate derivative <br />
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**[[3tq0]] – LmDHOD + fumarate <br />
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**[[4ef8]], [[4ef9]] – LmDHOD + cyanate derivative<br />
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* Dihydroorotate dehydrogenase (quinone)
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**[[1f76]] – DHODH + orotate – ''Escherichia coli''<br />
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**[[3kvj]], [[3kvk]], [[3kvl]], [[3kvm]] – hDHODH + inhibitor - human<br />
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**[[1d3h]] – hDHODH + orotate + cell growth retarding drug <br />
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**[[4igh]] - hDHODH + quinoline derivative<br />
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**[[3f1q]], [[3fj6]], [[3fjl]], [[3g0u]], [[3g0x]] – hDHODH + orotate + leflunomide<br />
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**[[3w7r]], [[3u2o]], [[3zws]], [[3zwt]], [[4jgd]], [[4js3]], [[4jts]], [[1d3g]], [[1uuo]], [[2b0m]], [[2fpt]], [[2fpv]], [[2fpy]], [[2fqi]], [[2wv8]], [[4jtt]], [[4jtu]], [[4ls0]], [[4ls1]], [[4ls2]], [[4oqv]], [[4rk8]], [[4rka]], [[4rli]], [[4rr4]], [[4ylw]], [[4zl1]], [[4zmg]], [[5h2z]], [[5hin]], [[5hqe]], [[5k9c]], [[5k9d]], [[5mut]], [[5mvc]], [[5mvd]], [[5h73]] – hDHODH + orotate + inhibitor<br />
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**[[2prl]], [[2prm]], [[2prh]] – hDHODH (mutant) + orotate + inhibitor<br />
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**[[6et4]] – hDHODH + FMN + inhibitor<br />
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**[[4ori]] – rDHODH + orotate + inhibitor - rat<br />
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**[[1uum]] – rDHODH + orotate + drug<br />
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**[[1tv5]], [[3i65]], [[3i68]], [[3i6r]], [[3o8a]], [[3sfk]], [[4cq8]], [[4cq9]], [[4cqa]], [[4orm]], [[4rx0]], [[5boo]], [[5fi8]] – PfDHODH + orotate + inhibitor – ''Plasmodium falciparum''<br />
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**[[5del]], [[5tbo]] – PfDHODH (mutant) + orotate + inhibitor <br />
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**[[6b8s]] – DHODH + FMN – ''Helicobacter pylori''<br />
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* Dihydroorotate dehydrogenase (fumarate)
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**[[3w6y]], [[3w70]], [[3w71]], [[3w70]], [[3w71]], [[3w72]], [[3w73]], [[3w74]], [[3w75]], [[3w76]], [[3w7c]], [[3w7d]], [[3w7e]], [[3w7g]], [[3w7h]], [[3w7i]], [[3w7j]], [[3w7k]], [[3w7l]], [[3w7m]], [[3w7n]], [[3w7o]], [[3w7p]], [[3w7q]], [[3w83]], [[3w84]], [[3w85]], [[3w86]], [[3w87]], [[3w88]], [[4jd4]], [[4jdb]], [[3w1q]], [[3w1r]], [[3w1t]], [[3w1u]], [[3w1x]], [[3w22]], [[3w23]], [[3w2j]], [[3w2k]], [[3w2l]], [[3w2m]], [[3w2n]], [[3w2u]], [[3w3o]], [[5e93]], [[5ea9]] – TcDHODF + inhibitor<br />
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**[[3w1p]] - TcDHODF + pyrimidine derivative<br />
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**[[3w1a]], [[3w1l]], [[3w1m]], [[3w1n]] - TcDHODF + orotate derivative<br />
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**[[5xfw]] - TbDHODF (mutant) + malonate<br />
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**[[5xfv]] - TbDHODF (mutant) + FMN + malonate<br />
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}}
 
== References ==
== References ==
<references/>
<references/>
[[Category:Topic Page]]
[[Category:Topic Page]]

Current revision

Human dihydroorotate dehydrogenase with FMN complex with orotate and inhibitor brequinar (PDB entry 2b0m)

Drag the structure with the mouse to rotate

References

  1. ↑ Munier-Lehmann H, Vidalain PO, Tangy F, Janin YL. On dihydroorotate dehydrogenases and their inhibitors and uses. J Med Chem. 2013 Apr 25;56(8):3148-67. doi: 10.1021/jm301848w. Epub 2013 Mar 20. PMID:23452331 doi:http://dx.doi.org/10.1021/jm301848w
  2. ↑ Baumann P, Mandl-Weber S, Volkl A, Adam C, Bumeder I, Oduncu F, Schmidmaier R. Dihydroorotate dehydrogenase inhibitor A771726 (leflunomide) induces apoptosis and diminishes proliferation of multiple myeloma cells. Mol Cancer Ther. 2009 Feb;8(2):366-75. doi: 10.1158/1535-7163.MCT-08-0664. Epub, 2009 Jan 27. PMID:19174558 doi:http://dx.doi.org/10.1158/1535-7163.MCT-08-0664
  3. ↑ Hurt DE, Sutton AE, Clardy J. Brequinar derivatives and species-specific drug design for dihydroorotate dehydrogenase. Bioorg Med Chem Lett. 2006 Mar 15;16(6):1610-5. Epub 2006 Jan 10. PMID:16406782 doi:S0960-894X(05)01599-4

Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky, Joel L. Sussman

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