Functional Analysis of Protein Kinase CK2 of the Human Malaria Parasite Plasmodium falciparum

Protein kinase CK2 (casein kinase 2) is a eukaryotic serine/threonine protein kinase with multiple substrates and roles in diverse cellular processes, including differentiation, proliferation, and translation. The mammalian holoenzyme consists of two catalytic alpha or alpha' subunits and two regulatory beta subunits. We report the identification and characterization of a Plasmodium falciparum CK2 alpha orthologue, PfCK2 alpha, and two PfCK2 beta orthologues, PfCK2 beta 1 and PfCK2 beta 2. Recombinant PfCK2 alpha possesses protein kinase activity, exhibits similar substrate and cosubstrate preferences to those of CK2 alpha subunits from other organisms, and interacts with both of the PfCK2 beta subunits in vitro. Gene disruption experiments show that the presence of PfCK2 alpha is crucial to asexual blood stage parasites and thereby validate the enzyme as a possible drug target. PfCK2 alpha is amenable to inhibitor screening, and we report differential susceptibility between the human and P. falciparum CK2 alpha enzymes to a small molecule inhibitor. Taken together, our data identify PfCK2 alpha as a potential target for antimalarial chemotherapeutic intervention.