cGMP-dependent protein kinase (Plasmodium falciparum) (PfPKG)

Plasmodium falciparum protein kinase G (PfPKG) is a cyclic guanosine monophosphate (cGMP)-dependent serine/threonine protein kinase that serves as a master regulator of the malaria parasite's life cycle (UniProt Q8I534). It is essential for critical developmental transitions, including the egress of merozoites from infected erythrocytes, the activation of gametocytes in the mosquito midgut, and the invasion of hepatocytes by sporozoites (Baker et al., 2017; Frontiers in Cellular and Infection Microbiology, 2020). PfPKG functions by integrating cGMP signaling with calcium release and phosphoinositide metabolism, thereby coordinating the complex cellular processes required for parasite survival and transmission (PLOS Pathogens, 2014). As a therapeutic target, PfPKG is highly attractive because its inhibition can potentially provide curative, prophylactic, and transmission-blocking effects (Nature Communications, 2017). Current drug discovery efforts focus on developing potent, ATP-competitive inhibitors, such as imidazopyridines (e.g., ML-10) and thiazoles, while ensuring high selectivity over human PKG to minimize host toxicity (PNAS, 2019; Journal of Medicinal Chemistry, 2020).

Other names

Protein kinase GPfPKGcGMP-dependent protein kinase 1PKG

ATP-competitive inhibition of the kinase domain