5XVU

Crystal structure of the protein kinase CK2 catalytic domain from Plasmodium falciparum bound to ATP

5XVU の概要

• エントリーDOI: 10.2210/pdb5xvu/pdb
• 分子名称: Casein kinase 2, alpha subunit, SULFATE ION, CHLORIDE ION, ... (7 entities in total)
• 機能のキーワード: casein kinase 2 plasmodium falciparum kinase, transferase
• 由来する生物種: Plasmodium falciparum (isolate 3D7)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 121577.53

構造登録者

El Sahili, A.,Lescar, J.,Ruiz-Carrillo, D.,Lin, J.Q. (登録日: 2017-06-28, 公開日: 2017-07-12, 最終更新日: 2023-11-22)

主引用文献

Ruiz-Carrillo, D.,Lin, J.Q.,El Sahili, A.,Wei, M.,Sze, S.K.,Cheung, P.C.F.,Doerig, C.,Lescar, J.
The protein kinase CK2 catalytic domain from Plasmodium falciparum: crystal structure, tyrosine kinase activity and inhibition.
Sci Rep, 8:7365-7365, 2018

PubMed Abstract: Malaria causes every year over half-a-million deaths. The emergence of parasites resistant to available treatments makes the identification of new targets and their inhibitors an urgent task for the development of novel anti-malaria drugs. Protein kinase CK2 is an evolutionary-conserved eukaryotic serine/threonine protein kinase that in Plasmodium falciparum (PfCK2) has been characterized as a promising target for chemotherapeutic intervention against malaria. Here we report a crystallographic structure of the catalytic domain of PfCK2α (D179S inactive single mutant) in complex with ATP at a resolution of 3.0 Å. Compared to the human enzyme, the structure reveals a subtly altered ATP binding pocket comprising five substitutions in the vicinity of the adenine base, that together with potential allosteric sites, could be exploited to design novel inhibitors specifically targeting the Plasmodium enzyme. We provide evidence for the dual autophosphorylation of residues Thr and Tyr of PfCK2. We also show that CX4945, a human CK2 inhibitor in clinical trials against solid tumor cancers, is effective against PfCK2 with an IC of 13.2 nM.

PubMed: 29743645
DOI: 10.1038/s41598-018-25738-5

実験手法

X-RAY DIFFRACTION (3 Å)