English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

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  ( Pf CK2) has been characterized as a promising target for chemotherapeutic intervention against malaria. Here we report a crystallographic structure of the catalytic domain of  Pf CK2α (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 63  and Tyr 30  of  Pf CK2. We also show that CX4945, a human CK2 inhibitor in clinical trials against solid tumor cancers, is effective against  Pf CK2 with an IC 50  of 13.2 nM.

The protein kinase CK2 catalytic domain from Plasmodium falciparum: crystal structure, tyrosine kinase activity and inhibition