Protein kinase CK2 in health and disease: Structural bases of protein kinase CK2 inhibition.
Protein kinase CK2 is involved in many fundamental aspects of normal cell life, but it is also able to establish favourable conditions for tumorigenesis. CK2 is elevated in various cancers, it is a potent suppressor of apoptosis, it strongly promotes cell survival, it strengthens the multi-drug resistant phenotype and can be considered a valuable drug target for cancer therapy. In this review, the structural bases of CK2 inhibition deduced from the analysis of crystal structures of CK2alpha-inhibitor complexes are presented and discussed. The best ATP-competitive inhibitors show an adequate hydrophobic character, an excellent shape complementarity with the unique active site of CK2, and the ability to establish polar interactions with both the hinge region and the positive electrostatic area near the conserved water W1 and the Lys68-Glu81 salt bridge. The state of the art of non-ATP-competitive inhibitors is also presented.
Battistutta
R
R
Department of Chemical Sciences and Venetian Institute of Molecular Medicine (VIMM), University of Padua, via Marzolo 1, 35131, Padua, Italy. roberto.battistutta@unipd.it
D000255:Adenosine Triphosphate / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D047390:Casein Kinase II / Q000037:antagonists & inhibitors* / Q000737:chemistry; D020134:Catalytic Domain; D002986:Clinical Trials as Topic; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D000255:Adenosine Triphosphate; D047390:Casein Kinase II