The dihydroorotate dehydrogenases: Past and present.
Arch Biochem Biophys
; 632: 175-191, 2017 10 15.
Article
in En
| MEDLINE
| ID: mdl-28666740
ABSTRACT
The flavoenzyme dihydroorotate dehydrogenase catalyzes the stereoselective oxidation of (S)-dihydroorotate to orotate in the fourth of the six conserved enzymatic reactions involved in the de novo pyrimidine biosynthetic pathway. Inhibition of pyrimidine metabolism by selectively targeting DHODHs has been exploited in the development of new therapies against cancer, immunological disorders, bacterial and viral infections, and parasitic diseases. Through a chronological narrative, this review summarizes the efforts of the scientific community to achieve our current understanding of structural and biochemical properties of DHODHs. It also attempts to describe the latest advances in medicinal chemistry for therapeutic development based on the selective inhibition of DHODH, including an overview of the experimental techniques used for ligand screening during the process of drug discovery.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Oxidoreductases Acting on CH-CH Group Donors
/
Flavoproteins
Limits:
Animals
/
Humans
Language:
En
Year:
2017
Type:
Article