Niefind, Karsten, Bischoff, Nils, Golub, Andriy G., Bdzhola, Volodymyr G., Balanda, Anatoliy O., Prykhod'ko, Andriy O., Yarmoluk, Sergiy M., Niefind, Karsten, Bischoff, Nils, Golub, Andriy G., Bdzhola, Volodymyr G., Balanda, Anatoliy O., Prykhod'ko, Andriy O., and Yarmoluk, Sergiy M.
Protein kinase CK2 is associated with a number of human diseases, among them cancer, and is therefore a target for inhibitor development in industry and academia. Six crystal structures of either CK2 alpha, the catalytic subunit of human protein kinase CK2, or its paralog CK2 alpha' in complex with two ATP-competitive inhibitors-based on either a flavonol or a thieno[2,3-d]pyrimidine framework-are presented. The structures show examples for extreme structural deformations of the ATP-binding loop and its neighbourhood and of the hinge/helix alpha D region, i.e., of two zones of the broader ATP site environment. Thus, they supplement our picture of the conformational space available for CK2 alpha and CK2 alpha'. Further, they document the potential of synthetic ligands to trap unusual conformations of the enzymes and allow to envision a new generation of inhibitors that stabilize such conformations.