5JI8

Crystal structure of the BRD9 bromodomain and hit 1

5JI8 の概要

• エントリーDOI: 10.2210/pdb5ji8/pdb
• 分子名称: Bromodomain-containing protein 9, 2-amino-1,3-benzothiazole-6-carboxamide (3 entities in total)
• 機能のキーワード: brd9, bromodomain, protein binding
• 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: 13250.41

構造登録者

Wang, N.,Li, F.,Bao, H.,Li, J.,Wu, J.,Ruan, K. (登録日: 2016-04-22, 公開日: 2016-06-22, 最終更新日: 2023-11-08)

主引用文献

Wang, N.,Li, F.,Bao, H.,Li, J.,Wu, J.,Ruan, K.
NMR Fragment Screening Hit Induces Plasticity of BRD7/9 Bromodomains
Chembiochem, 17:1456-1463, 2016

PubMed Abstract: The complex biology associated with inhibition of bromodomain and extra-terminal (BET) domains by chemical probes has attracted increasing attention, and there is a need to identify non-BET bromodomain (BD) inhibitors. Several potent inhibitors of the BRD9 BD have recently been discovered, with anticancer and anti-inflammation activity. However, its paralogue, BRD7 BD, remains unexploited. Here, we identified new chemotypes targeting BRD7 BD by using NMR fragment-based screening. BRD7/9 BDs exhibit similar patterns of chemical-shift perturbation upon the titration of hit compound 1. The crystal structure revealed that 1 repels the Y222 group of BRD9 BD in a similar way to that for butyryllysine, but not acetyllysine and known inhibitors. Hit 1 induced less rearrangement of residue F161 of BRD9 BD than acetyllysine, butyryllysine, and crotonyllysine. Our study provides structural insight into a new generation of butyryllysine mimics for probing the function of BRD7/9 BD.

PubMed: 27194508
DOI: 10.1002/cbic.201600184

実験手法

X-RAY DIFFRACTION (1.42 Å)