dc.contributor.authorRuiz-Carrillo, David
dc.contributor.authorLin, Jianqing
dc.contributor.authorEl Sahili, Abbas
dc.contributor.authorWei, Meng
dc.contributor.authorSze, Siu Kwan
dc.contributor.authorCheung, Peter Ching For
dc.contributor.authorDoerig, Christian
dc.contributor.authorLescar, Julien
dc.date.accessioned2018-07-27T05:55:45Z
dc.date.available2018-07-27T05:55:45Z
dc.date.issued2018
dc.identifier.citationRuiz-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-.en_US
dc.identifier.issn2045-2322en_US
dc.identifier.urihttp://hdl.handle.net/10220/45318
dc.description.abstractMalaria 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.en_US
dc.description.sponsorshipMOE (Min. of Education, S’pore)en_US
dc.format.extent12 p.en_US
dc.language.isoenen_US
dc.relation.ispartofseriesScientific Reportsen_US
dc.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/.en_US
dc.subjectProtein Kinase CK2en_US
dc.subjectMalariaen_US
dc.titleThe protein kinase CK2 catalytic domain from Plasmodium falciparum : crystal structure, tyrosine kinase activity and inhibitionen_US
dc.typeJournal Article
dc.contributor.researchNTU Institute of Structural Biologyen_US
dc.contributor.schoolSchool of Biological Sciencesen_US
dc.identifier.doihttp://dx.doi.org/10.1038/s41598-018-25738-5
dc.description.versionPublished versionen_US


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