Download MendeleyStructural Hypervariability of the Two Human Protein Kinase CK2 Catalytic Subunit Paralogs Revealed by Complex Structures with a Flavonol- and a Thieno[2,3-d]pyrimidine-Based Inhibitor.
Niefind, K., Bischoff, N., Golub, A.G., Bdzhola, V.G., Balanda, A.O., Prykhod'ko, A.O., Yarmoluk, S.M.(2017) Pharmaceuticals (Basel) 10
- PubMed: 28085026
- DOI: https://doi.org/10.3390/ph10010009
- Primary Citation of Related Structures:
5M44, 5M4C, 5M4F, 5M4I, 5M4U, 5M56 - PubMed Abstract:
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¦Á, the catalytic subunit of human protein kinase CK2, or its paralog CK2¦Á' 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 ¦ÁD region, i.e., of two zones of the broader ATP site environment. Thus, they supplement our picture of the conformational space available for CK2¦Á and CK2¦Á'. 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.
Organizational Affiliation:
Department f¨¹r Chemie, Institut f¨¹r Biochemie, Universit?t zu K?ln, Otto-Fischer-Stra?e 12-14, D-50674 K?ln, Germany. Karsten.Niefind@uni-koeln.de.
