5EGU

FIRST DOMAIN OF HUMAN BROMODOMAIN BRD4 IN COMPLEX WITH INHIBITOR 3-Butyl-8-(6-butyl-5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-ylsulfanylmethyl)-7-ethyl-3,7-dihydropurine-2,6-dione

5EGU の概要

• エントリーDOI: 10.2210/pdb5egu/pdb
• 分子名称: Bromodomain-containing protein 4, 3-butyl-8-[(6-butyl-5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)sulfanylmethyl]-7-ethyl-purine-2,6-dione, 1,2-ETHANEDIOL, ... (4 entities in total)
• 機能のキーワード: inhibitor, histone, epigenetic reader, bromodomain, brd4, brd4_bd1, brd4_bd1 06-nov, transcription
• 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: 4
• 化学式量合計: 62398.06

構造登録者

Raux, B.,Rebuffet, E.,Betzi, S.,Priet, S.,Morelli, X. (登録日: 2015-10-27, 公開日: 2016-01-20, 最終更新日: 2024-01-10)

主引用文献

Raux, B.,Voitovich, Y.,Derviaux, C.,Lugari, A.,Rebuffet, E.,Milhas, S.,Priet, S.,Roux, T.,Trinquet, E.,Guillemot, J.C.,Knapp, S.,Brunel, J.M.,Fedorov, A.Y.,Collette, Y.,Roche, P.,Betzi, S.,Combes, S.,Morelli, X.
Exploring Selective Inhibition of the First Bromodomain of the Human Bromodomain and Extra-terminal Domain (BET) Proteins.
J.Med.Chem., 59:1634-1641, 2016

PubMed Abstract: A midthroughput screening follow-up program targeting the first bromodomain of the human BRD4 protein, BRD4(BD1), identified an acetylated-mimic xanthine derivative inhibitor. This compound binds with an affinity in the low micromolar range yet exerts suitable unexpected selectivity in vitro against the other members of the bromodomain and extra-terminal domain (BET) family. A structure-based program pinpointed a role of the ZA loop, paving the way for the development of potent and selective BET-BRDi probes.

PubMed: 26735842
DOI: 10.1021/acs.jmedchem.5b01708

実験手法

X-RAY DIFFRACTION (2.21 Å)