5DEL

Crystal structure of Plasmodium falciparum dihydroorotate dehydrogenase bound with Inhibitor DSM59

Replaces:  4RYH

Summary for 5DEL

• Entry DOI: 10.2210/pdb5del/pdb
• Descriptor: Dihydroorotate dehydrogenase (quinone), mitochondrial, FLAVIN MONONUCLEOTIDE, OROTIC ACID, ... (7 entities in total)
• Functional Keywords: alpha/beta barrel, mitochondrial membrane, fmn, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor
• Biological source: Plasmodium falciparum
• Cellular location: Mitochondrion inner membrane ; Single-pass membrane protein : Q08210
• Total number of polymer chains: 1
• Total formula weight: 46737.09

Authors

Phillips, M.,Deng, X. (deposition date: 2015-08-25, release date: 2015-10-07, Last modification date: 2023-09-27)

Primary citation

Deng, X.,Matthews, D.,Rathod, P.K.,Phillips, M.A.
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.,Sect.F, 71:553-559, 2015

PubMed Abstract: 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 Å 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.

PubMed: 25945708
DOI: 10.1107/S2053230X15000989

Experimental method

X-RAY DIFFRACTION (2.2 Å)