4PCE

Crystal Structure of the first bromodomain of human BRD4 in complex with compound B13

4PCE の概要

• エントリーDOI: 10.2210/pdb4pce/pdb
• 関連するPDBエントリー: 4PCI
• 分子名称: Bromodomain-containing protein 4, 1,2-ETHANEDIOL, 1-benzyl-2-ethyl-1,5,6,7-tetrahydro-4H-indol-4-one, ... (4 entities in total)
• 機能のキーワード: transcription-transcription inhibitor complex, transcription/transcription inhibitor
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Nucleus: O60885
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 15414.79

構造登録者

Dong, J.,Caflisch, A. (登録日: 2014-04-15, 公開日: 2014-05-07, 最終更新日: 2023-12-27)

主引用文献

Zhao, H.,Gartenmann, L.,Dong, J.,Spiliotopoulos, D.,Caflisch, A.
Discovery of BRD4 bromodomain inhibitors by fragment-based high-throughput docking.
Bioorg.Med.Chem.Lett., 24:2493-2496, 2014

PubMed Abstract: Bromodomains (BRDs) recognize acetyl-lysine modified histone tails mediating epigenetic processes. BRD4, a protein containing two bromodomains, has emerged as an attractive therapeutic target for several types of cancer as well as inflammatory diseases. Using a fragment-based in silico screening approach, we identified two small molecules that bind to the first bromodomain of BRD4 with low-micromolar affinity and favorable ligand efficiency (0.37 kcal/mol per non-hydrogen atom), selectively over other families of bromodomains. Notably, the hit rate of the fragment-based in silico approach is about 10% as only 24 putative inhibitors, from an initial library of about 9 million molecules, were tested in vitro.

PubMed: 24767840
DOI: 10.1016/j.bmcl.2014.04.017

実験手法

X-RAY DIFFRACTION (1.293 Å)