6A1C

Crystal structure of the CK2a1-go289 complex

6A1C の概要

• エントリーDOI: 10.2210/pdb6a1c/pdb
• 分子名称: Casein kinase II subunit alpha, 5-bromanyl-2-methoxy-4-[(E)-(3-methylsulfanyl-5-phenyl-1,2,4-triazol-4-yl)iminomethyl]phenol, SODIUM ION, ... (5 entities in total)
• 機能のキーワード: ck2a1, inhibitor, complex, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 42534.24

構造登録者

Kinoshita, T.,Tsuyuguchi, M. (登録日: 2018-06-07, 公開日: 2019-03-06, 最終更新日: 2023-11-22)

主引用文献

Oshima, T.,Niwa, Y.,Kuwata, K.,Srivastava, A.,Hyoda, T.,Tsuchiya, Y.,Kumagai, M.,Tsuyuguchi, M.,Tamaru, T.,Sugiyama, A.,Ono, N.,Zolboot, N.,Aikawa, Y.,Oishi, S.,Nonami, A.,Arai, F.,Hagihara, S.,Yamaguchi, J.,Tama, F.,Kunisaki, Y.,Yagita, K.,Ikeda, M.,Kinoshita, T.,Kay, S.A.,Itami, K.,Hirota, T.
Cell-based screen identifies a new potent and highly selective CK2 inhibitor for modulation of circadian rhythms and cancer cell growth.
Sci Adv, 5:eaau9060-eaau9060, 2019

PubMed Abstract: Compounds targeting the circadian clock have been identified as potential treatments for clock-related diseases, including cancer. Our cell-based phenotypic screen revealed uncharacterized clock-modulating compounds. Through affinity-based target deconvolution, we identified GO289, which strongly lengthened circadian period, as a potent and selective inhibitor of CK2. Phosphoproteomics identified multiple phosphorylation sites inhibited by GO289 on clock proteins, including PER2 S693. Furthermore, GO289 exhibited cell type-dependent inhibition of cancer cell growth that correlated with cellular clock function. The x-ray crystal structure of the CK2α-GO289 complex revealed critical interactions between GO289 and CK2-specific residues and no direct interaction of GO289 with the hinge region that is highly conserved among kinases. The discovery of GO289 provides a direct link between the circadian clock and cancer regulation and reveals unique design principles underlying kinase selectivity.

PubMed: 30746467
DOI: 10.1126/sciadv.aau9060

実験手法

X-RAY DIFFRACTION (1.68 Å)