Toxoplasma gondii calcium-dependent protein kinase 3 (TgCDPK3) (TgCDPK3)

Toxoplasma gondii calcium-dependent protein kinase 3 (TgCDPK3) is a key regulator of the lytic cycle in the protozoan parasite Toxoplasma gondii, the causative agent of toxoplasmosis (Lourido et al., 2012, Science). It acts as a calcium-responsive switch that triggers the rapid egress of parasites from host cells and facilitates gliding motility, both of which are essential for the dissemination of the infection (McCoy et al., 2012, Science). Since calcium-dependent protein kinases (CDPKs) are found in apicomplexan parasites but are absent in mammals, TgCDPK3 serves as a highly selective therapeutic target (Sibley et al., 2013, Nature Reviews Microbiology). Small molecule inhibitors known as bumped kinase inhibitors (BKIs), such as BKI-1294, have been developed to exploit the unique architecture of the TgCDPK3 ATP-binding pocket, which contains a small glycine gatekeeper residue (Ojo et al., 2014, J Infect Dis). Inhibition of TgCDPK3 effectively traps the parasite within the host cell, preventing further tissue damage and disease progression.

Other names

CDPK3Calcium-dependent protein kinase 3TGME49_216630TGGT1_216630TgCPK3

Inhibition of kinase activity by competitive binding to the ATP-binding site, specifically exploiting the small gatekeeper residue (Glycine 128) to achieve selectivity over host kinases (Ojo et al., 2014, J Infect Dis).