Open Access Articles- Top Results for Dihydroorotate dehydrogenase

Dihydroorotate dehydrogenase

Dihydroorotate oxidase
EC number
CAS number 9029-03-2
IntEnz IntEnz view
ExPASy NiceZyme view
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO
Dihydroorotate dehydrogenase from E. coli
Symbol DHO_dh
Pfam PF01180
InterPro IPR001295
SCOP 1dor
OPM superfamily 59
OPM protein 1uum
CDD cd02810
Human dihydroorotate dehydrogenase
Symbol DHODH
Entrez 1723
HUGO 2867
OMIM 126064
RefSeq NM_001361
UniProt Q02127
Other data
EC number
Locus Chr. 16 q22

Dihydroorotate dehydrogenase (EC is an enzyme that catalyzes the fourth step in the de novo biosynthesis of pyrimidine. It catalyses the oxidation of dihydroorotate to orotate:

(S)-dihydroorotate + O2 <math>\rightleftharpoons</math> orotate + H2O2

Human dihydroorotate dehydrogenase is a ubiquitous FMN flavoprotein. In bacteria (gene pyrD), it is located on the inner side of the cytosolic membrane. In some yeasts, such as in Saccharomyces cerevisiae (gene URA1), it is a cytosolic protein, whereas, in other eukaryotes, it is found in the mitochondria.[1]

Clinical significance

The immunomodulatory drugs teriflunomide and leflunomide have been shown to inhibit DHODH. Human DHODH has two domains: an alpha/beta-barrel domain containing the active site and an alpha-helical domain that forms the opening of a tunnel leading to the active site. Leflunomide has been shown to bind in this tunnel.[2] Leflunomide is being used for treatment of rheumatoid and psoriatic arthritis.

Mutations in this gene have been shown to cause Miller syndrome [3] also known as Genee-Wiedemann syndrome, Wildervanck-Smith syndrome or post axial acrofacial dystosis (POADS).

Model organisms

Model organisms have been used in the study of DHODH function. A conditional knockout mouse line called Dhodhtm1b(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute.[4] Male and female animals underwent a standardized phenotypic screen[5] to determine the effects of deletion.[6][7][8][9] Additional screens performed: - In-depth immunological phenotyping[10]



  1. ^ Lacroute F, Thomas D, Nagy M (1992). "Divergent evolution of pyrimidine biosynthesis between anaerobic and aerobic yeasts". Proc. Natl. Acad. Sci. U.S.A. 89 (19): 8966–70. PMC 50045. PMID 1409592. doi:10.1073/pnas.89.19.8966. 
  2. ^ Liu S, Neidhardt EA, Grossman TH, Ocain T, Clardy J (January 2000). "Structures of human dihydroorotate dehydrogenase in complex with antiproliferative agents". Structure 8 (1): 25–33. PMID 10673429. doi:10.1016/S0969-2126(00)00077-0. 
  3. ^ Ng SB, Buckingham KJ,Lee C, Bigham AW, Tabor HK, Dent KM, Huff CD, Shannon PT, Jabs EW, Nickerson DA, Shendure J, Bamshad MJ (December 2009). "Exome Sequencing identifies the cause of a mendelian disorder". Nature Genetics 42 (1): 30–5. PMC 2847889. PMID 19915526. doi:10.1038/ng.499. 
  4. ^ Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Opthalmologica 88: 925-7.doi:10.1111/j.1755-3768.2010.4142.x: Wiley. 
  5. ^ a b "International Mouse Phenotyping Consortium". 
  6. ^ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V et al. (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–42. PMC 3572410. PMID 21677750. doi:10.1038/nature10163. 
  7. ^ Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. PMID 21677718. doi:10.1038/474262a. 
  8. ^ Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell 128 (1): 9–13. PMID 17218247. doi:10.1016/j.cell.2006.12.018. 
  9. ^ White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN et al. (2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell 154 (2): 452–64. PMID 23870131. doi:10.1016/j.cell.2013.06.022. 
  10. ^ a b "Infection and Immunity Immunophenotyping (3i) Consortium". 

Further reading

External links

Template:Nucleotide metabolism

This article incorporates text from the public domain Pfam and InterPro IPR001295

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