Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41598-018-25738-5
DC FieldValue
dc.titleThe protein kinase CK2 catalytic domain from Plasmodium falciparum: Crystal structure, tyrosine kinase activity and inhibition
dc.contributor.authorRuiz-Carrillo, D
dc.contributor.authorLin, J
dc.contributor.authorEl Sahili, A
dc.contributor.authorWei, M
dc.contributor.authorSze, S.K
dc.contributor.authorCheung, P.C.F
dc.contributor.authorDoerig, C
dc.contributor.authorLescar, J
dc.date.accessioned2020-10-20T09:49:39Z
dc.date.available2020-10-20T09:49:39Z
dc.date.issued2018
dc.identifier.citationRuiz-Carrillo, D, Lin, J, El Sahili, A, Wei, M, Sze, S.K, Cheung, P.C.F, Doerig, C, Lescar, J (2018). The protein kinase CK2 catalytic domain from Plasmodium falciparum: Crystal structure, tyrosine kinase activity and inhibition. Scientific Reports 8 (1) : 7365. ScholarBank@NUS Repository. https://doi.org/10.1038/s41598-018-25738-5
dc.identifier.issn2045-2322
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/178413
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 PfCK2? (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. © 2018 The Author(s).
dc.publisherNature Publishing Group
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceUnpaywall 20201031
dc.subjectcasein kinase II
dc.subjectprotein kinase inhibitor
dc.subjectprotein tyrosine kinase
dc.subjectamino acid sequence
dc.subjectchemistry
dc.subjectenzyme active site
dc.subjectenzymology
dc.subjectgene expression regulation
dc.subjectgenetics
dc.subjectmetabolism
dc.subjectmolecular model
dc.subjectmutation
dc.subjectphosphorylation
dc.subjectPlasmodium falciparum
dc.subjectX ray crystallography
dc.subjectAmino Acid Sequence
dc.subjectCasein Kinase II
dc.subjectCatalytic Domain
dc.subjectCrystallography, X-Ray
dc.subjectGene Expression Regulation, Enzymologic
dc.subjectModels, Molecular
dc.subjectMutation
dc.subjectPhosphorylation
dc.subjectPlasmodium falciparum
dc.subjectProtein Kinase Inhibitors
dc.subjectProtein-Tyrosine Kinases
dc.typeArticle
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.description.doi10.1038/s41598-018-25738-5
dc.description.sourcetitleScientific Reports
dc.description.volume8
dc.description.issue1
dc.description.page7365
dc.published.statepublished
Appears in Collections:Staff Publications
Elements

Show simple item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_1038_s41598-018-25738-5.pdf2.09 MBAdobe PDF

OPEN

NoneView/Download

Google ScholarTM

Check

Altmetric


This item is licensed under a Creative Commons License Creative Commons