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.

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Relevance

Leflunomide and brequinar are anti-rheumatic drugs which bind to DHOD^[2].

Structural highlights

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3D Structures of dihydroorotate dehydrogenase

Dihydroorotate dehydrogenase 3D structures

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

Drag the structure with the mouse to rotate

ReferencesReferences

↑ 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
↑ 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
↑ 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

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Michal Harel, Alexander Berchansky, Joel L. Sussman

[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

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