Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1) (PfCDPK1)

Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1) is a vital enzyme in the life cycle of the malaria parasite, specifically during the erythrocytic stage (UniProt: Q8I4V8). It functions as a calcium-regulated molecular switch that coordinates the egress of merozoites from host red blood cells and their subsequent invasion of new cells (PubMed: 20624296). The enzyme's structure is unique, featuring a kinase domain linked to a calmodulin-like domain, a configuration absent in human kinases, which makes it an attractive target for selective inhibition (PubMed: 24415839). PfCDPK1 phosphorylates key components of the parasite's actomyosin motor, such as the glideosome-associated protein 45 (GAP45), facilitating motility and host cell entry (PubMed: 23028330). Small-molecule inhibitors, particularly bumped kinase inhibitors (BKIs), have demonstrated potent antimalarial activity by targeting the glycine gatekeeper residue in the ATP-binding pocket (PubMed: 25135273). Targeting PfCDPK1 offers a promising strategy to disrupt the parasite's replication cycle and combat drug-resistant malaria strains.

Other names

CDPK1Calcium-dependent protein kinase 1PF3D7_0217500PFB0815w

Inhibition of the kinase activity by binding to the ATP-binding pocket, thereby preventing the phosphorylation of substrates required for parasite egress and invasion.