Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/32720
Title: Malaria Protein Kinase CK2 (PfCK2) Shows Novel Mechanisms of Regulation
Authors: Graciotti, Michele
Alam, Mahmood
Solyakov, Lev
Schmid, Ralf
Burley, G.
Bottrill, Andrew R.
Doerig, C.
Cullis, Paul
Tobin, Andrew B.
First Published: 21-Mar-2014
Publisher: Public Library of Science
Citation: PLoS One, 2014, 9 (3), e85391
Abstract: Casein kinase 2 (protein kinase CK2) is a conserved eukaryotic serine/theronine kinase with multiple substrates and roles in the regulation of cellular processes such as cellular stress, cell proliferation and apoptosis. Here we report a detailed analysis of the Plasmodium falciparum CK2, PfCK2, demonstrating that this kinase, like the mammalian orthologue, is a dual specificity kinase able to phosphorylate at both serine and tyrosine. However, unlike the human orthologue that is auto-phosphorylated on tyrosine within the activation loop, PfCK2 shows no activation loop auto-phosphorylation but rather is auto-phosphorylated at threonine 63 within subdomain I. Phosphorylation at this site in PfCK2 is shown here to regulate the intrinsic kinase activity of PfCK2. Furthermore, we generate an homology model of PfCK2 in complex with the known selective protein kinase CK2 inhibitor, quinalizarin, and in so doing identify key co-ordinating residues in the ATP binding pocket that could aid in designing selective inhibitors to PfCK2.
DOI Link: 10.1371/journal.pone.0085391
eISSN: 1932-6203
Links: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0085391
http://hdl.handle.net/2381/32720
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2014 Graciotti et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Appears in Collections:Published Articles, Dept. of Cell Physiology and Pharmacology

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