Plasmodium vivax cGMP-dependent protein kinase (PvPKG)

Plasmodium vivax cGMP-dependent protein kinase (PvPKG) is a central signaling enzyme that regulates critical transitions throughout the complex life cycle of the malaria parasite. As a serine/threonine kinase activated by the secondary messenger cyclic GMP (cGMP), it acts as a master switch for processes including the egress of parasites from host red blood cells and hepatocytes, the invasion of new host cells, and the development of sexual stages required for transmission to mosquitoes. PvPKG is structurally distinct from its human orthologs, possessing four cGMP-binding domains and a smaller 'gatekeeper' residue in its ATP-binding pocket, which provides a unique structural vulnerability for drug design. Small-molecule inhibitors, such as the imidazopyridine ML10, have demonstrated high selectivity and potency by binding to this specific pocket, effectively blocking multiple stages of infection. Because it is essential for both the symptomatic blood stage and the transmission-enabling sexual stages, PvPKG is a high-priority target for developing antimalarials with both curative and transmission-blocking potential. Its role in liver-stage development also suggests utility in prophylactic strategies to prevent the establishment of infection.

Other names

Protein kinase GcGMP-dependent protein kinasePvPKGPKG

ATP-competitive inhibition of the kinase domain, which prevents the phosphorylation of downstream substrates and disrupts cGMP-mediated signaling pathways essential for parasite egress, invasion, and differentiation.