6GMD

The crystal structure of CK2alpha in complex with compound 3

6GMD の概要

• エントリーDOI: 10.2210/pdb6gmd/pdb
• 分子名称: Casein kinase II subunit alpha, ACETATE ION, [3-chloranyl-4-(2-propan-2-ylphenyl)phenyl]methylazanium, ... (5 entities in total)
• 機能のキーワード: ck2alpha, ck2a, fragment based drug discovery, high concentration screening, selective atp competitive inhibitors, surface entrophy reduction, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 84968.47

構造登録者

Brear, P.,Iegre, J.,North, A.,De Fusco, C.,Georgiou, K.,Lubin, A.,Carro, L.,Sore, H.,Hyvonen, M.,Spring, D. (登録日: 2018-05-25, 公開日: 2018-06-06, 最終更新日: 2024-01-17)

主引用文献

Brear, P.,North, A.,Iegre, J.,Hadje Georgiou, K.,Lubin, A.,Carro, L.,Green, W.,Sore, H.F.,Hyvonen, M.,Spring, D.R.
Novel non-ATP competitive small molecules targeting the CK2 alpha / beta interface.
Bioorg. Med. Chem., 26:3016-3020, 2018

PubMed Abstract: Increased CK2 levels are prevalent in many cancers. Combined with the critical role CK2 plays in many cell-signaling pathways, this makes it a prime target for down regulation to fight tumour growth. Herein, we report a fragment-based approach to inhibiting the interaction between CK2α and CK2β at the α-β interface of the holoenzyme. A fragment, CAM187, with an IC of 44 μM and a molecular weight of only 257 gmol has been identified as the most promising compound. Importantly, the lead fragment only bound at the interface and was not observed in the ATP binding site of the protein when co-crystallised with CK2α. The fragment-like molecules discovered in this study represent unique scaffolds to CK2 inhibition and leave room for further optimisation.

PubMed: 29759799
DOI: 10.1016/j.bmc.2018.05.011

実験手法

X-RAY DIFFRACTION (1.66 Å)