F
IPR012135

Dihydroorotate dehydrogenase, class 1/ 2

InterPro entry
Short nameDihydroorotate_DH_1_2
Overlapping
homologous
superfamilies
 
family relationships

Description

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
[1]
.

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
[2]
. 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
[3]
. 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 α helical domain
[4, 5]
. These enzymes use respiratory quinones as the physiological electron acceptor.

References

1.Active site of dihydroorotate dehydrogenase A from Lactococcus lactis investigated by chemical modification and mutagenesis. Bjornberg O, Rowland P, Larsen S, Jensen KF. Biochemistry 36, 16197-205, (1997). View articlePMID: 9405053

2.The crystal structure of Lactococcus lactis dihydroorotate dehydrogenase A complexed with the enzyme reaction product throws light on its enzymatic function. Rowland P, Bjornberg O, Nielsen FS, Jensen KF, Larsen S. Protein Sci. 7, 1269-79, (1998). View articlePMID: 9655329

3.Structure of dihydroorotate dehydrogenase B: electron transfer between two flavin groups bridged by an iron-sulphur cluster. Rowland P, Norager S, Jensen KF, Larsen S. Structure 8, 1227-38, (2000). View articlePMID: 11188687

4.Structures of human dihydroorotate dehydrogenase in complex with antiproliferative agents. Liu S, Neidhardt EA, Grossman TH, Ocain T, Clardy J. Structure 8, 25-33, (2000). View articlePMID: 10673429

5.E. coli dihydroorotate dehydrogenase reveals structural and functional distinctions between different classes of dihydroorotate dehydrogenases. Norager S, Jensen KF, Bjornberg O, Larsen S. Structure 10, 1211-23, (2002). View articlePMID: 12220493

GO terms

cellular component

  • None

Cross References

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