Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/86831
Title: The protein kinase CK2 catalytic domain from Plasmodium falciparum : crystal structure, tyrosine kinase activity and inhibition
Authors: Ruiz-Carrillo, David
Lin, Jianqing
El Sahili, Abbas
Wei, Meng
Sze, Siu Kwan
Doerig, Christian
Lescar, Julien
Cheung, Peter Ching For
Keywords: Protein Kinase CK2
Malaria
Issue Date: 2018
Source: Ruiz-Carrillo, D., Lin, J., El Sahili, A., Wei, M., Sze, S. K., Cheung, P. C. F., et al. (2018). The protein kinase CK2 catalytic domain from Plasmodium falciparum : crystal structure, tyrosine kinase activity and inhibition. Scientific Reports, 8(1), 7365-.
Series/Report no.: Scientific Reports
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 Thr63 and Tyr30 of PfCK2. We also show that CX4945, a human CK2 inhibitor in clinical trials against solid tumor cancers, is effective against PfCK2 with an IC50 of 13.2 nM.
URI: https://hdl.handle.net/10356/86831
http://hdl.handle.net/10220/45318
ISSN: 2045-2322
DOI: 10.1038/s41598-018-25738-5
Rights: © 2018 The Author(s) (Nature Publishing Group). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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