Structural highlights
Function
[PYRD_PLAF7] Catalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor.
Publication Abstract from PubMed
Plasmodium species are protozoan parasites that are the causative agent of malaria. Malaria is a devastating disease, and its treatment and control have been hampered by the propensity of the parasite to become drug-resistant. Dihydroorotate dehydrogenase (DHODH) has been identified as a promising new target for the development of antimalarial agents. Here, the X-ray structure of P. falciparum DHODH bound to a potent and selective N-phenylbenzamide-based inhibitor (DSM59) is described at 2.3 A resolution. The structure elucidates novel binding-site interactions and shows how conformational flexibility of the enzyme leads to the ability to bind diverse chemical structures with high affinity. This information provides new insight into the design of high-affinity DHODH inhibitors for the treatment of malaria.
The X-ray structure of Plasmodium falciparum dihydroorotate dehydrogenase bound to a potent and selective N-phenylbenzamide inhibitor reveals novel binding-site interactions.,Deng X, Matthews D, Rathod PK, Phillips MA Acta Crystallogr F Struct Biol Commun. 2015 May;71(Pt 5):553-9. doi:, 10.1107/S2053230X15000989. Epub 2015 Apr 21. PMID:25945708[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Deng X, Matthews D, Rathod PK, Phillips MA. The X-ray structure of Plasmodium falciparum dihydroorotate dehydrogenase bound to a potent and selective N-phenylbenzamide inhibitor reveals novel binding-site interactions. Acta Crystallogr F Struct Biol Commun. 2015 May;71(Pt 5):553-9. doi:, 10.1107/S2053230X15000989. Epub 2015 Apr 21. PMID:25945708 doi:http://dx.doi.org/10.1107/S2053230X15000989
