Dihydroorotate dehydrogenase, class 1 (IPR024920)

Short name: Dihydroorotate_DH_1

Overlapping homologous superfamilies

Family relationships


Dihydroorotate dehydrogenase (DHOD), also known as dihydroorotate oxidase, catalyses the fourth step in de novo pyrimidine biosynthesis, the stereospecific oxidation of (S)-dihydroorotate to orotate, which is the only redox reaction in this pathway. DHODs can be divided into two mains classes: class 1 cytosolic enzymes found primarily in Gram-positive bacteria, and class 2 membrane-associated enzymes found primarily in eukaryotic mitochondria and Gram-negative bacteria [PMID: 9405053].

The class 1 DHODs can be further divided into subclasses 1A and 1B, which differ in their structural organisation and use of electron acceptors. The 1A enzyme is a homodimer of two PyrD subunits where each subunit forms a TIM barrel fold with a bound FMN cofactor located near the top of the barrel [PMID: 9655329]. Fumarate is the natural electron acceptor for this enzyme. The 1B enzyme, in contrast is a heterotetramer composed of a central, FMN-containing, PyrD homodimer resembling the 1A homodimer, and two additional PyrK subunits which contain FAD and a 2Fe-2S cluster [PMID: 11188687]. These additional groups allow the enzyme to use NAD(+) as its natural electron acceptor.

The class 2 membrane-associated enzymes are monomers which have the FMN-containing TIM barrel domain found in the class 1 PyrD subunit, and an additional N-terminal alpha helical domain [PMID: 10673429, PMID: 12220493]. These enzymes use respiratory quinones as the physiological electron acceptor.

This entry represents the class 1 enzymes. It includes both type 1B, which uses NAD+ as electron acceptor and 1A, which uses instead fumarate as the electron acceptor [PMID: 8021180].

GO terms

Biological Process

GO:0006221 pyrimidine nucleotide biosynthetic process

Molecular Function

GO:0004152 dihydroorotate dehydrogenase activity

Cellular Component

GO:0005737 cytoplasm

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.