Calcium-dependent protein kinase 1 (CDPK1)

Calcium-dependent protein kinase 1 (CDPK1) is a crucial signaling enzyme found in apicomplexan parasites, including Plasmodium falciparum (the causative agent of malaria) and Toxoplasma gondii, but is absent in humans (UniProt: Q8I0W1). It functions as a calcium-sensor that directly couples calcium signals to the phosphorylation of substrates involved in parasite motility, host cell invasion, and egress from infected cells (PubMed: 20445537). Structurally, CDPK1 is unique because it contains a calmodulin-like domain within the same polypeptide chain as the kinase domain, allowing for direct activation by calcium (PubMed: 24415839). This enzyme is a major therapeutic target because its ATP-binding pocket features a small gatekeeper residue (typically glycine or serine), which is rare in human kinases, allowing for the design of highly selective bumped kinase inhibitors (BKIs) (PubMed: 25154543). Inhibition of CDPK1 effectively halts the parasite life cycle, making it a promising candidate for treating parasitic infections (PubMed: 30224518).

Other names

CDPK1PfCDPK1TgCDPK1Calcium-dependent protein kinase 1 (Plasmodium falciparum)Calcium-dependent protein kinase 1 (Toxoplasma gondii)

Inhibition of the kinase catalytic activity by binding to the ATP-binding pocket, specifically exploiting the small gatekeeper residue to achieve selectivity over host kinases (PubMed: 25154543).