9HKS

Protein Kinase CK2 and small molecule ligands

This is a non-PDB format compatible entry.

Summary for 9HKS

• Entry DOI: 10.2210/pdb9hks/pdb
• Descriptor: Casein kinase II subunit alpha, SULFATE ION, 2-(5-chloranyl-1~{H}-indol-3-yl)ethanamide, ... (4 entities in total)
• Functional Keywords: protein kinase ck2 fragment ligand, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 87106.28

Authors

Krimm, I.,Gelin, M.,Guichou, J.F. (deposition date: 2024-12-04, release date: 2025-07-30)

Primary citation

Grenier, D.,Gelin, M.,Yang, Y.,Mularoni, A.,Guichou, J.F.,Delcros, J.G.,Krimm, I.
Binding-Site Switch for Protein Kinase CK2 Inhibitors.
Chemmedchem, 20:e202400868-e202400868, 2025

PubMed Abstract: The serine/threonine protein kinase CK2, a tetramer composed of a regulatory dimer (CK2β) bound to two catalytic subunits CK2α, is a well-established therapeutic target for various pathologies, including cancer and viral infections. Several types of CK2 inhibitors have been developed, including inhibitors that bind to the catalytic ATP-site, bivalent inhibitors that occupy both the CK2α ATP-site and the αD pocket, and inhibitors that target the CK2α/CK2β interface. Interestingly, the bivalent inhibitor AB668 shares a similar chemical structure with the interface inhibitor CCH507. In this study, we designed analogs of CCH507 using structure-based and fragment-based approaches. The ability of these analogs to bind the CK2α/CK2β interface was evaluated using biolayer interferometry and fluorescence anisotropy-based assays. Their potency to inhibit CK2 kinase activity was determined using the bioluminescent ADP-Glo assay. These experiments allowed us to investigate which chemical modifications prevent the binding of the compounds at the CK2α/CK2β interface. Seven out of sixteen compounds conserved the ability to bind at the protein-protein interface, among which three compounds exhibited better interface inhibition compared to CCH507.

PubMed: 39835439
DOI: 10.1002/cmdc.202400868

Experimental method

X-RAY DIFFRACTION (2.4 Å)