Dihydroorotate dehydrogenase
| Dihydroorotate oxidase | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| EC number | 1.3.3.1 | ||||||
| CAS number | 9029-03-2 | ||||||
| Databases | |||||||
| IntEnz | IntEnz view | ||||||
| BRENDA | BRENDA entry | ||||||
| ExPASy | NiceZyme view | ||||||
| KEGG | KEGG entry | ||||||
| MetaCyc | metabolic pathway | ||||||
| PRIAM | profile | ||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||
| Gene Ontology | AmiGO / EGO | ||||||
|
|||||||
 |
|||||||||
| Dihydroorotate dehydrogenase from E. coli | |||||||||
| Identifiers | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Symbol | DHO_dh | ||||||||
| Pfam | PF01180 | ||||||||
| InterPro | IPR001295 | ||||||||
| PROSITE | PDOC00708 | ||||||||
| SCOP | 1dor | ||||||||
| SUPERFAMILY | 1dor | ||||||||
| OPM family | 59 | ||||||||
| OPM protein | 1uum | ||||||||
|
|||||||||
| Identifiers | |
|---|---|
| Symbol | DHODH |
| Entrez | 1723 |
| HUGO | 2867 |
| OMIM | 126064 |
| PDB | 1D3G |
| RefSeq | NM_001361 |
| UniProt | Q02127 |
| Other data | |
| EC number | 1.3.3.1 |
| Locus | Chr. 16 q22 |
Dihydroorotate dehydrogenase (EC 1.3.3.1) is an enzyme that catalyzes the fourth step in the de novo biosynthesis of pyrimidine. It converts dihydroorotate to orotate:
- (S)-dihydroorotate + O2
orotate + H2O2
orotate + H2O2-
Orotic acid. Note the double bond in the ring.
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]
Contents |
[edit] Human proteins containing this domain
[edit] Clinical significance
The anti-inflammatory drug leflunomide has 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).
[edit] References
- ^ 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. doi:10.1073/pnas.89.19.8966. PMC 50045. PMID 1409592. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=50045.
- ^ 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. doi:10.1016/S0969-2126(00)00077-0. PMID 10673429.
- ^ 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. doi:10.1038/ng.499. PMC 2847889. PMID 19915526. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2847889.
[edit] Further reading
- Rowland P, Björnberg O, Nielsen FS, Jensen KF, Larsen S (June 1998). "The crystal structure of Lactococcus lactis dihydroorotate dehydrogenase A complexed with the enzyme reaction product throws light on its enzymatic function". Protein Sci. 7 (6): 1269–79. doi:10.1002/pro.5560070601. PMC 2144028. PMID 9655329. http://www.proteinscience.org/cgi/content/abstract/7/6/1269.
[edit] External links
|
|||||||||||||||||
|
|||||||||||||||||||||||||||||
This article incorporates text from the public domain Pfam and InterPro IPR001295
| This oxidoreductase article is a stub. You can help Wikipedia by expanding it. |
