2A94

Structure of Plasmodium falciparum lactate dehydrogenase complexed to APADH.

2A94 の概要

• エントリーDOI: 10.2210/pdb2a94/pdb
• 分子名称: L-lactate dehydrogenase, ACETYL PYRIDINE ADENINE DINUCLEOTIDE, REDUCED (3 entities in total)
• 機能のキーワード: rossmann fold, oxidoreductase
• 由来する生物種: Plasmodium falciparum (malaria parasite P. falciparum)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 35510.84

構造登録者

Chaikuad, A.,Fairweather, V.,Conners, R.,Joseph-Horne, T.,Turgut-Balik, D.,Brady, R.L. (登録日: 2005-07-11, 公開日: 2006-01-10, 最終更新日: 2023-09-20)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.5 Å)