Toxoplasma gondii calcium-dependent protein kinase 1 (TGME49_101440), in complex with inhibitor PCI-32765

Calcium-dependent protein kinases (CDPKs) are found only in specific plants and apicomplexan parasites. Some parasite CDPKs contain a small residue (glycine, serine or threonine) in the gatekeeper position. This makes these kinases particularly sensitive to a class of inhibitors designed for tyrosine kinase inhibitors. We have co-crystallized a number of such compounds with Toxoplasma CDPK1, which contains a glycine gatekeeper. Herein, we present TgCDPK1 with ibrutinib (also known as PCI-32765), which is FDA approved for treating mantle cell lymphoma and a covalent inhibitor of bruton tyrosine kinase (BTK). We have also co-crystallized this kinase with other compounds (4IHP, 4IH8 and 4IEB).