Dihydroorotate dehydrogenase

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Revision as of 08:43, 10 June 2019

spinqualitylabelsall models Human dihydroorotate dehydrogenase with FMN complex with orotate and inhibitor brequinar (PDB entry 2b0m) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image Contents 1 Function 2 Relevance 3 Structural highlights 4 3D Structures of dihydroorotate dehydrogenase Function Dihydroorotate dehydrogenase (DHOD) catalyzes the conversion of dihydroorotate to orotate. DHOD (quinone) (DHODH) or DHOD mitochondrial catalyzes the conversion of dihydroorotate and quinone to orotate and quinol. DHOD (fumarate) (DHODF) catalyzes the conversion of dihydroorotate and fumarate to orotate and succinate. DHOD is part of the biosynthesis of pyrimidine. FMN is the cofactor in this reaction. [1] Relevance Leflunomide and brequinar are anti-rheumatic drugs which bind to DHOD[2]. Structural highlights . The . See also this . [3] 3D Structures of dihydroorotate dehydrogenase Dihydroorotate dehydrogenase 3D structures

3D Structures of dihydroorotate dehydrogenase

Updated on 10-June-2019 {{#tree:id=OrganizedByTopic|openlevels=0|

• Dihydroorotate dehydrogenase

• • 1dor, 1jue – LlDHOD A – Lactococcus lactis
    
  • 1jub – LlDHOD A (mutant)
    
  • 1ep1, 1ep3 – LlDHOD B
    
  • 5ksw – LlDHOD A+B (mutant)
    
  • 2djx, 3c3n – TcDHOD – Trypanosoma cruzi
    
  • 3tjx, 3tro, 6tgx – LmDHOD (mutant) – Leishmania major
    
  • 4wzh – DHOD – Leishmania braziliensis
    
  • 4zq6 – DHOD – Mycobacterium tuberculosis
    
  • 4ylf, 4yry – DHOD A+B – Thermotoga maritima
    
  • 6b8s – DHODH + FMN – Helicobacter pylori
    

• DHOD binary complex

• • 3kvj, 3kvk, 3kvl, 3kvm – hDHOD + inhibitor - human
    
  • 2bxv – hDHOD + orotate
    
  • 2e68 – hDHOD + dihydroorotate
    
  • 2dor - LlDHOD A + orotate
    
  • 1jqv, 1jqx, 1jrb, 1jrc, 1ovd – LlDHOD A (mutant) + orotate
    
  • 2bsl, 2bx7 – LlDHOD A + pyrimidine analog
    
  • 1ep2, 1ue9 – LlDHOD B+ orotate
    
  • 2djl – TcDHOD + succinate
    
  • 2e6a - TcDHOD + orotate derivative
    
  • 2e6d – TcDHOD + fumarate
    
  • 2e6f – TcDHOD + oxonate
    
  • 2b4g – TbDHOD + orotate – Trypanosoma brucei
    
  • 3c61 – DHOD + orotate – Leishmania donovani
    
  • 3mhu, 3mjy – LmDHOD + orotate derivative
    
  • 3tq0 – LmDHOD + fumarate
    
  • 4ef8, 4ef9 – LmDHOD + cyanate derivative
    

• Dihydroorotate dehydrogenase (quinone)

• • 3kvj, 3kvk, 3kvl, 3kvm – hDHODH + inhibitor
    
  • 1d3h – hDHODH + orotate + cell growth retarding drug
    
  • 4igh - hDHODH + quinoline derivative
    
  • 3f1q, 3fj6, 3fjl, 3g0u, 3g0x – hDHODH + orotate + leflunomide
    
  • 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, 5h735zf9, 6cjg, 6et4, 5zf4, 5zf7, 5zf8, 5zfa, 5zfb, 6cjf, 6fmd, [[6qu7] – hDHODH + orotate + inhibitor
    
  • 2prl, 2prm, 2prh – hDHODH (mutant) + orotate + inhibitor
    
  • 6et4 – hDHODH + FMN + inhibitor
    
  • 4ori – rDHODH + orotate + inhibitor - rat
    
  • 1uum – rDHODH + orotate + drug
    
  • 1tv5, 3i65, 3i68, 3i6r, 3o8a, 3sfk, 4cq8, 4cq9, 4cqa, 4orm, 4rx0, 5boo, 5fi8, 6i55, 6gjg, 6i4b - PfDHODH + orotate + inhibitor – Plasmodium falciparum
    
  • 5del, 5tbo, 6e0b – PfDHODH (mutant) + orotate + inhibitor
    
  • 1f76 – DHODH + orotate – Escherichia coli
    

• Dihydroorotate dehydrogenase (fumarate)

• • 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
    
  • 3w1p - TcDHODF + pyrimidine derivative
    
  • 3w1a, 3w1l, 3w1m, 3w1n - TcDHODF + orotate derivative
    
  • 5xfw - TbDHODF (mutant) + malonate
    
  • 5xfv - TbDHODF (mutant) + FMN + malonate
    

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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