7A4C

Crystal structure of human protein kinase CK2alpha (CSNK2A1 gene product) in complex with the ATP-competitive inhibitor 5,6,7-tribromo-1H-triazolo[4,5-b]pyridine

7A4C の概要

• エントリーDOI: 10.2210/pdb7a4c/pdb
• 関連するPDBエントリー: 7A22 7A49
• 分子名称: Casein kinase II subunit alpha, 5,6,7-tris(bromanyl)-1~{H}-[1,2,3]triazolo[4,5-b]pyridine, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: protein kinase ck2, casein kinase 2, atp-competitive inhibitor, 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: 81699.74

構造登録者

Niefind, K.,Lindenblatt, D.,Toelzer, C.,Bretner, M.,Chojnacki, K.,Wielechowska, M.,Winska, P. (登録日: 2020-08-19, 公開日: 2020-12-09, 最終更新日: 2024-01-31)

主引用文献

Chojnacki, K.,Lindenblatt, D.,Winska, P.,Wielechowska, M.,Toelzer, C.,Niefind, K.,Bretner, M.
Synthesis, biological properties and structural study of new halogenated azolo[4,5-b]pyridines as inhibitors of CK2 kinase.
Bioorg.Chem., 106:104502-104502, 2021

PubMed Abstract: The new halogenated 1H-triazolo[4,5-b]pyridines and 1H-imidazo[4,5-b]pyridines were synthesised as analogues of known CK2 inhibitors: 4,5,6,7-tetrabromo-1H-benzotriazole (TBBt) and 4,5,6,7-tetrabromo-1H-benzimidazole (TBBi). Their influence on the activity of recombinant human CK2α, CK2α' and PIM1 kinases was determined. The most active inhibitors were di- and trihalogenated 1H-triazolo[4,5-b]pyridines (4a, 5a and 10a) with IC values 2.56, 3.82 and 3.26 μM respectively for CK2α. Furthermore, effect on viability of cancer cell lines MCF-7 (human breast adenocarcinoma) and CCRF-CEM (T lymphoblast leukemia) of all final compounds was evaluated. Finally, three crystal structures of complexes of CK2α with inhibitors 4a, 5a and 10a were obtained. In addition, new protocol was used to obtain high-resolution crystal structures of CK2α' in complex with four inhibitors (4a, 5a, 5b, 10a).

PubMed: 33317841
DOI: 10.1016/j.bioorg.2020.104502

実験手法

X-RAY DIFFRACTION (2.502 Å)