Molecular and Cellular Biochemistry

, Volume 316, Issue 1, pp 57–62

A structural insight into CK2 inhibition


  • Marco Mazzorana
    • Department of Biological ChemistryUniversity of Padua
    • Venetian Institute of Molecular Medicine (VIMM)
  • Lorenzo A. Pinna
    • Department of Biological ChemistryUniversity of Padua
    • Venetian Institute of Molecular Medicine (VIMM)
    • Venetian Institute of Molecular Medicine (VIMM)
    • Department of Chemical Sciences University of Padua

DOI: 10.1007/s11010-008-9822-5

Cite this article as:
Mazzorana, M., Pinna, L.A. & Battistutta, R. Mol Cell Biochem (2008) 316: 57. doi:10.1007/s11010-008-9822-5


The acidophilic Ser/Thr protein kinase CK2 displays some unique properties such as high pleiotropicity and constitutive activity. CK2 is involved in many fundamental aspects of the normal cell life, for instance it promotes cell survival and enhances the tumour phenotype under special circumstances. This makes CK2 an appealing target for the development of inhibitors with pharmacological potential. Here we present an overview of our recent studies on inhibitors directed to the CK2 ATP-binding site whose distinctive features are highlighted by the ability to use both ATP and GTP as co-substrates and by its low susceptibility to staurosporine inhibition. We discuss the effects of the binding of different chemical families of fairly selective inhibitors with potency in the nanomolar or low micromolar range. An important common energetic contribution to the binding is due to the hydrophobic interaction with the apolar surface region of the CK2 binding cleft. The analysis of the known CK2 crystal structures reveals the presence of some highly conserved water molecules in this region. These waters reside near Lys68, in an area with a positive electrostatic potential that is able to attract and orient negatively charged ligands. The presence of this positive region and of two unique bulky residues, Ile66 and Ile174, responsible for the reduced dimension of the CK2 active site, play a critical role in determining ligand orientation and binding selectivity.


Protein kinase CK2ATP-binding siteStructural propertiesCompetitive inhibitorsEnergy of binding

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© Springer Science+Business Media, LLC. 2008