5M4C

Complex structure of human protein kinase CK2 catalytic subunit with a thieno[2,3-d]pyrimidin inhibitor crystallized under low-salt conditions

Summary for 5M4C

• Entry DOI: 10.2210/pdb5m4c/pdb
• Related: 5M44
• Descriptor: Casein kinase II subunit alpha, 3-[5-(4-methylphenyl)thieno[2,3-d]pyrimidin-4-yl]sulfanylpropanoic acid, CHLORIDE ION, ... (5 entities in total)
• Functional Keywords: protein kinase ck2, casein kinase 2, transferase
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus : P68400
• Total number of polymer chains: 1
• Total formula weight: 40616.81

Authors

Niefind, K.,Bischoff, N.,Yarmoluk, S.M.,Bdzhola, V.G.,Golub, A.G.,Balanda, A.O.,Prykhod'ko, A.O. (deposition date: 2016-10-18, release date: 2017-01-18, Last modification date: 2024-01-17)

Primary citation

Niefind, K.,Bischoff, N.,Golub, A.G.,Bdzhola, V.G.,Balanda, A.O.,Prykhod'ko, A.O.,Yarmoluk, S.M.
Structural 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.
Pharmaceuticals, 10:-, 2017

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 CK2α, the catalytic subunit of human protein kinase CK2, or its paralog CK2α' 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 αD region, i.e., of two zones of the broader ATP site environment. Thus, they supplement our picture of the conformational space available for CK2α and CK2α'. 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.

PubMed: 28085026
DOI: 10.3390/ph10010009

Experimental method

X-RAY DIFFRACTION (1.935 Å)