Phosphatidylinositol 4-kinase beta (Plasmodium vivax) (PvPI4Kβ)

Phosphatidylinositol 4-kinase beta (PI4Kβ) is a vital lipid kinase in the malaria parasite Plasmodium vivax, responsible for the synthesis of phosphatidylinositol 4-phosphate (PI4P). This enzyme is essential across multiple stages of the parasite's life cycle, including the liver (exo-erythrocytic) and blood (erythrocytic) stages, where it regulates critical processes such as membrane trafficking and the formation of the parasitophorous vacuole (McNamara et al., Nature, 2013). By controlling the availability of PI4P, PI4Kβ facilitates cytokinesis and the biogenesis of new membranes required for daughter cell formation. In Plasmodium vivax specifically, this target is of high interest because its inhibition can potentially clear dormant hypnozoites, which are responsible for disease relapse (Paquet et al., Sci Transl Med, 2017). Small-molecule inhibitors like MMV390048 have demonstrated potent antimalarial activity by binding to the ATP-binding pocket of the enzyme, leading to a rapid depletion of PI4P and subsequent parasite death. However, a significant challenge in drug development is achieving sufficient selectivity to avoid inhibiting the human PI4Kβ ortholog, which is involved in essential host cellular functions such as Golgi signaling.

Other names

PI4KIIIbetaPI4KIIIbPhosphatidylinositol 4-kinase type III betaPI4K-betaPvPI4K

ATP-competitive inhibition of the kinase domain, preventing the phosphorylation of phosphatidylinositol to phosphatidylinositol 4-phosphate (PI4P).