4CFK

N-TERMINAL BROMODOMAIN OF HUMAN BRD4 WITH LY294002

4CFK の概要

• エントリーDOI: 10.2210/pdb4cfk/pdb
• 関連するPDBエントリー: 4CFL
• 分子名称: BRD4 PROTEIN, GLYCEROL, 2-MORPHOLIN-4-YL-7-PHENYL-4H-CHROMEN-4-ONE, ... (5 entities in total)
• 機能のキーワード: cell cycle, inhibitor, histone, epigenetic reader, antagonist
• 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: 15560.88

構造登録者

Chung, C.,Dittmann, A.,Drewes, G. (登録日: 2013-11-18, 公開日: 2014-01-15, 最終更新日: 2024-05-08)

主引用文献

Dittmann, A.,Werner, T.,Chung, C.,Savitski, M.M.,Falth Savitski, M.,Grandi, P.,Hopf, C.,Lindon, M.,Neubauer, G.,Prinjha, R.K.,Bantscheff, M.,Drewes, G.
The Commonly Used Pi3-Kinase Probe Ly294002 is an Inhibitor of Bet Bromodomains.
Acs Chem.Biol., 9:495-, 2014

PubMed Abstract: A commonly used small-molecule probe in cell-signaling research is the phosphoinositide 3-kinase inhibitor LY294002. Quantitative chemoproteomic profiling shows that LY294002 and LY303511, a close analogue devoid of PI3K activity, inhibit the BET bromodomain proteins BRD2, BRD3, and BRD4 that comprise a family of targets structurally unrelated to PI3K. Both compounds competitively inhibit acetyl-lysine binding of the first but not the second bromodomain of BET proteins in cell extracts. X-ray crystallography shows that the chromen-4-one scaffold represents a new bromodomain pharmacophore and establishes LY294002 as a dual kinase and BET-bromodomain inhibitor, whereas LY303511 exhibits anti-inflammatory and antiproliferative effects similar to the recently discovered BET inhibitors.

PubMed: 24533473
DOI: 10.1021/CB400789E

実験手法

X-RAY DIFFRACTION (1.55 Å)