Structural highlights
Publication Abstract from PubMed
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.
Pyruvate kinase from Plasmodium falciparum: Structural and kinetic insights into the allosteric mechanism.,Zhong W, Li K, Cai Q, Guo J, Yuan M, Wong YH, Walkinshaw MD, Fothergill-Gilmore LA, Michels PAM, Dedon PC, Lescar J Biochem Biophys Res Commun. 2020 Aug 30. pii: S0006-291X(20)31645-4. doi:, 10.1016/j.bbrc.2020.08.048. PMID:32878705[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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References
- ↑ Zhong W, Li K, Cai Q, Guo J, Yuan M, Wong YH, Walkinshaw MD, Fothergill-Gilmore LA, Michels PAM, Dedon PC, Lescar J. Pyruvate kinase from Plasmodium falciparum: Structural and kinetic insights into the allosteric mechanism. Biochem Biophys Res Commun. 2020 Aug 30. pii: S0006-291X(20)31645-4. doi:, 10.1016/j.bbrc.2020.08.048. PMID:32878705 doi:https://dx.doi.org/10.1016/j.bbrc.2020.08.048
