4RLL

Crystal structure of human CK2alpha in complex with the ATP-competitive inhibitor 4-[(E)-(fluoren-9-ylidenehydrazinylidene)-methyl] benzoate

4RLL の概要

• エントリーDOI: 10.2210/pdb4rll/pdb
• 関連するPDBエントリー: 4RLK
• 分子名称: Casein kinase II subunit alpha, GLYCEROL, 4-[(E)-(9H-fluoren-9-ylidenehydrazinylidene)methyl]benzoic acid, ... (4 entities in total)
• 機能のキーワード: transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 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: 40485.18

構造登録者

Guerra, B.,Rasmussen, T.D.L.,Schnitzler, A.,Jensen, H.H.,Boldyreff, B.S.,Miyata, Y.,Marcussen, N.,Niefind, K.,Issinger, O.G. (登録日: 2014-10-17, 公開日: 2014-12-17, 最終更新日: 2023-09-20)

主引用文献

Guerra, B.,Rasmussen, T.D.,Schnitzler, A.,Jensen, H.H.,Boldyreff, B.S.,Miyata, Y.,Marcussen, N.,Niefind, K.,Issinger, O.G.
Protein kinase CK2 inhibition is associated with the destabilization of HIF-1 alpha in human cancer cells.
Cancer Lett, 356:751-761, 2015

PubMed Abstract: Screening for protein kinase CK2 inhibitors of the structural diversity compound library (DTP NCI/NIH) led to the discovery of 4-[(E)-(fluoren-9-ylidenehydrazinylidene)-methyl]benzoic acid (E9). E9 induces apoptotic cell death in various cancer cell lines and upon hypoxia, the compound suppresses CK2-catalyzed HSP90/Cdc37 phosphorylation and induces HIF-1α degradation. Furthermore, E9 exerts a strong anti-tumour activity by inducing necrosis in murine xenograft models underlining its potential to be used for cancer treatment in future clinical studies. Crystal structure analysis of human and maize CK2α in complex with E9 reveals unique binding properties of the inhibitor to the enzyme, accounting for its affinity and selectivity.

PubMed: 25449433
DOI: 10.1016/j.canlet.2014.10.026

実験手法

X-RAY DIFFRACTION (1.85 Å)