Plasmodium falciparum cGMP-dependent protein kinase (PfPKG)

Plasmodium falciparum cGMP-dependent protein kinase (PfPKG) is a serine/threonine protein kinase that serves as the primary effector of cyclic GMP (cGMP) signaling in the malaria parasite [1.1.1, 1.3.1]. It plays an essential role across multiple stages of the Plasmodium life cycle, including the asexual erythrocytic stage, the sexual stage (gametogenesis), and the pre-erythrocytic liver stage [1.3.1, 1.3.2]. Specifically, PfPKG regulates the egress of merozoites and gametes from host erythrocytes, the invasion of hepatocytes by sporozoites, and the motility of ookinetes in the mosquito vector [1.3.3, 1.4.2]. The enzyme coordinates these processes by triggering calcium mobilization and regulating downstream pathways such as proteolysis and phosphoinositide metabolism [1.3.4, 1.4.2]. PfPKG is considered a highly attractive drug target because it is essential for parasite survival and transmission, and it possesses a distinct gatekeeper residue (Thr618) that allows for the development of selective inhibitors that do not affect human PKG isoforms [1.3.1, 1.4.3]. Small-molecule inhibitors like ML10 and Compound 1 have demonstrated potent antimalarial activity by competitively binding to the ATP-binding site of the parasite enzyme [1.4.3, 1.4.4].

Other names

Protein kinase GPKGPfPKGcGMP-dependent protein kinase

ATP-competitive inhibition of kinase activity