2AA3

Crystal structure of Plasmodium vivax lactate dehydrogenase complex with APADH

Summary for 2AA3

• Entry DOI: 10.2210/pdb2aa3/pdb
• Descriptor: L-lactate dehydrogenase, SULFATE ION, ACETYL PYRIDINE ADENINE DINUCLEOTIDE, REDUCED, ... (4 entities in total)
• Functional Keywords: rossmann fold, oxidoreductase
• Biological source: Plasmodium vivax (malaria parasite P. vivax)
• Total number of polymer chains: 4
• Total formula weight: 142684.42

Authors

Chaikuad, A.,Fairweather, V.,Conners, R.,Joseph-Horne, T.,Turgut-Balik, D.,Brady, R.L. (deposition date: 2005-07-13, release date: 2006-01-10, Last modification date: 2023-09-20)

Primary citation

Chaikuad, A.,Fairweather, V.,Conners, R.,Joseph-Horne, T.,Turgut-Balik, D.,Brady, R.L.
Structure of Lactate Dehydrogenase from Plasmodium vivax: Complexes with NADH and APADH.
Biochemistry, 44:16221-16228, 2005

PubMed Abstract: Malaria caused by Plasmodium vivax is a major cause of global morbidity and, in rare cases, mortality. Lactate dehydrogenase is an essential Plasmodium protein and, therefore, a potential antimalarial drug target. Ideally, drugs directed against this target would be effective against both major species of Plasmodium, P. falciparum and P. vivax. In this study, the crystal structure of the lactate dehydrogenase protein from P. vivax has been solved and is compared to the equivalent structure from the P. falciparum enzyme. The active sites and cofactor binding pockets of both enzymes are found to be highly similar and differentiate these enzymes from their human counterparts. These structures suggest effective inhibition of both enzymes should be readily achievable with a common inhibitor. The crystal structures of both enzymes have also been solved in complex with the synthetic cofactor APADH. The unusual cofactor binding site in these Plasmodium enzymes is found to readily accommodate both NADH and APADH, explaining why the Plasmodium enzymes retain enzymatic activity in the presence of this synthetic cofactor.

PubMed: 16331982
DOI: 10.1021/bi051416y

Experimental method

X-RAY DIFFRACTION (2.05 Å)