6KSH

Crystal structure of pyruvate kinase (PYK) from Plasmodium falciparum in complex with oxalate and ATP

6KSH の概要

• エントリーDOI: 10.2210/pdb6ksh/pdb
• 分子名称: Pyruvate kinase, MAGNESIUM ION, ADENOSINE-5'-TRIPHOSPHATE, ... (6 entities in total)
• 機能のキーワード: pyruvate kinase, glycolysis, tetramer, allostery, transferase
• 由来する生物種: Plasmodium falciparum (isolate 3D7)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 226663.68

構造登録者

Zhong, W.,Cai, Q.,Li, K.,Lescar, J.,Dedon, P.C. (登録日: 2019-08-23, 公開日: 2020-08-26, 最終更新日: 2023-11-22)

主引用文献

Zhong, W.,Li, K.,Cai, Q.,Guo, J.,Yuan, M.,Wong, Y.H.,Walkinshaw, M.D.,Fothergill-Gilmore, L.A.,Michels, P.A.M.,Dedon, P.C.,Lescar, J.
Pyruvate kinase from Plasmodium falciparum: Structural and kinetic insights into the allosteric mechanism.
Biochem.Biophys.Res.Commun., 532:370-376, 2020

PubMed Abstract: During its intra-erythrocytic growth phase, the malaria parasite Plasmodium falciparum relies heavily on glycolysis for its energy requirements. Pyruvate kinase (PYK) is essential for regulating glycolytic flux and for ATP production, yet the allosteric mechanism of P. falciparum PYK (PfPYK) remains poorly understood. Here we report the first crystal structure of PfPYK in complex with substrate analogues oxalate and the ATP product. Comparisons of PfPYK structures in the active R-state and inactive T-state reveal a 'rock-and-lock' allosteric mechanism regulated by rigid-body rotations of each subunit in the tetramer. Kinetic data and structural analysis indicate glucose 6-phosphate is an activator by increasing the apparent maximal velocity of the enzyme. Intriguingly, the trypanosome drug suramin inhibits PfPYK, which points to glycolysis as a set of potential therapeutic targets against malaria.

PubMed: 32878705
DOI: 10.1016/j.bbrc.2020.08.048

実験手法

X-RAY DIFFRACTION (2.6 Å)