Cyclic GMP-dependent protein kinase (PKG) (PKG)

Cyclic GMP-dependent protein kinase (PKG) is a master regulator of the Plasmodium life cycle, essential for both Plasmodium falciparum and Plasmodium vivax (UniProt Q966P0, A5K703) [1]. It acts as a key signaling hub that coordinates critical processes such as the egress of parasites from host red blood cells and hepatocytes, as well as the invasion of new host cells [2, 3]. Beyond the asexual blood stage, PKG is vital for sexual development, including gametogenesis and the transition of the parasite within the mosquito vector [3]. Because PKG is indispensable across multiple stages of the parasite's life cycle, it is considered a high-priority target for developing multistage antimalarial drugs [4]. Selective inhibition is achieved by targeting structural differences between the parasite enzyme and human PKG, particularly at the gatekeeper residue (T618 in PfPKG) within the ATP-binding pocket [2, 5]. Small molecule inhibitors, such as imidazopyridazines and trisubstituted pyrroles, have demonstrated the ability to block parasite progression and prevent transmission, making PKG a robust candidate for next-generation malaria therapies [4, 6].

Other names

PfPKGPvPKGProtein kinase GcGMP-dependent protein kinasePlasmodium falciparum cyclic GMP-dependent protein kinasePlasmodium vivax cyclic GMP-dependent protein kinase

ATP-competitive inhibition of cyclic GMP-dependent protein kinase activity