6KSH

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

Summary for 6KSH

• Entry DOI: 10.2210/pdb6ksh/pdb
• Descriptor: Pyruvate kinase, MAGNESIUM ION, ADENOSINE-5'-TRIPHOSPHATE, ... (6 entities in total)
• Functional Keywords: pyruvate kinase, glycolysis, tetramer, allostery, transferase
• Biological source: Plasmodium falciparum (isolate 3D7)
• Total number of polymer chains: 4
• Total formula weight: 226663.68

Authors

Zhong, W.,Cai, Q.,Li, K.,Lescar, J.,Dedon, P.C. (deposition date: 2019-08-23, release date: 2020-08-26, Last modification date: 2023-11-22)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.6 Å)