8BGC

Crystal structure of human Casein Kinase II subunit alpha (CK2a1) in complex with compound 2 (AA-CS-9-003)

Summary for 8BGC

• Entry DOI: 10.2210/pdb8bgc/pdb
• Descriptor: Casein kinase II subunit alpha, SULFATE ION, 5-[(phenylmethyl)amino]pyrimido[4,5-c]quinoline-8-carboxylic acid, ... (4 entities in total)
• Functional Keywords: ck2apha, kinase, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 82277.26

Authors

Kraemer, A.,Axtman, A.D.,Knapp, S.,Structural Genomics Consortium (SGC) (deposition date: 2022-10-27, release date: 2022-11-23, Last modification date: 2024-01-31)

Primary citation

Davis-Gilbert, Z.W.,Kramer, A.,Dunford, J.E.,Howell, S.,Senbabaoglu, F.,Wells, C.I.,Bashore, F.M.,Havener, T.M.,Smith, J.L.,Hossain, M.A.,Oppermann, U.,Drewry, D.H.,Axtman, A.D.
Discovery of a Potent and Selective Naphthyridine-Based Chemical Probe for Casein Kinase 2.
Acs Med.Chem.Lett., 14:432-441, 2023

PubMed Abstract: Naphthyridine-based inhibitors were synthesized to yield a potent and cell-active inhibitor of casein kinase 2 (CK2). Compound selectively inhibits CK2α and CK2α' when profiled broadly, thereby making it an exquisitely selective chemical probe for CK2. A negative control that is structurally related but lacks a key hinge-binding nitrogen () was designed on the basis of structural studies. Compound does not bind CK2α or CK2α' in cells and demonstrates excellent kinome-wide selectivity. Differential anticancer activity was observed when compound was profiled alongside a structurally distinct CK2 chemical probe: SGC-CK2-1. This naphthyridine-based chemical probe () represents one of the best available small molecule tools with which to interrogate biology mediated by CK2.

PubMed: 37077385
DOI: 10.1021/acsmedchemlett.2c00530

Experimental method

X-RAY DIFFRACTION (2.8 Å)