Dihydroorotate dehydrogenase (quinone)

Class 2 dihydroorotate dehydrogenases (DHOQO, EC 1.3.5.2) is an enzyme with systematic name (S)-dihydroorotate:quinone oxidoreductase.

Since the reaction catalyzed by DHOQOs is both part of the electron transport chain and the pyrimidine de novo synthesis, it has been explored as a possible target for cancer treatment, immunological disorders and bacterial/viral infections.

[6][7][8] Structurally, DHOQOs are organized in monomers which adopt a (βα)8 (eightfold beta alpha barrel) fold.

The N-terminal domain is composed of two amphipathic α-helices (αA – αB) which are responsible for the lipid membrane interaction.

This domain is responsible for the binding of the cofactor FMN (making these enzymes part of the Flavoprotein super-family) and the electron donor dihydroorotate, close to the 8 β-strand core.

Enzymatic reaction catalyzed by DHOQO. In green is represented the protein surface, sitting in the membrane (in gray)
DHOQO structure colored by domains: N-terminal (blue) and core domain (green).