The Full Wiki

Dihydroorotate dehydrogenase: Wikis

Advertisements

Note: Many of our articles have direct quotes from sources you can cite, within the Wikipedia article! This article doesn't yet, but we're working on it! See more info or our list of citable articles.

Encyclopedia

From Wikipedia, the free encyclopedia

Dihydroorotate oxidase
Identifiers
EC number 1.3.3.1
CAS number 9029-03-2
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures
Gene Ontology AmiGO / EGO
1f76.gif
Dihydroorotate dehydrogenase from E. coli
Identifiers
Symbol DHO_dh
Pfam PF01180
InterPro IPR001295
PROSITE PDOC00708
SCOP 1dor
OPM family 59
OPM protein 1uum
Human dihydroorotate dehydrogenase
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 \rightleftharpoons 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 while in other eukaryotes it is found in the mitochondria[1].

Contents

Human proteins containing this domain

DHODH; DPYD;

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).

References

  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): 8966–8970. doi:10.1073/pnas.89.19.8966. PMID 1409592.  
  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. doi:10.1016/S0969-2126(00)00077-0. PMID 10673429.  
  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): 30–35. PMID 19915526.  

Further reading

External links

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

Advertisements

Advertisements






Got something to say? Make a comment.
Your name
Your email address
Message