4QEU

Crystal structure of BRD2(BD2) mutant in free form

4QEU の概要

• エントリーDOI: 10.2210/pdb4qeu/pdb
• 関連するPDBエントリー: 4QEO 4QEP
• 分子名称: Bromodomain-containing protein 2, ACETATE ION, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: bromodomain-containing protein 2, kiaa9001, ring3, transcription regulation, transcription
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus : P25440
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 13484.47

構造登録者

Tallant, C.,Baud, M.,Lin-Shiao, E.,Chirgadze, D.Y.,Ciulli, A. (登録日: 2014-05-19, 公開日: 2014-10-29, 最終更新日: 2023-09-20)

主引用文献

Baud, M.G.,Lin-Shiao, E.,Cardote, T.,Tallant, C.,Pschibul, A.,Chan, K.H.,Zengerle, M.,Garcia, J.R.,Kwan, T.T.,Ferguson, F.M.,Ciulli, A.
Chemical biology. A bump-and-hole approach to engineer controlled selectivity of BET bromodomain chemical probes.
Science, 346:638-641, 2014

PubMed Abstract: Small molecules are useful tools for probing the biological function and therapeutic potential of individual proteins, but achieving selectivity is challenging when the target protein shares structural domains with other proteins. The Bromo and Extra-Terminal (BET) proteins have attracted interest because of their roles in transcriptional regulation, epigenetics, and cancer. The BET bromodomains (protein interaction modules that bind acetyl-lysine) have been targeted by potent small-molecule inhibitors, but these inhibitors lack selectivity for individual family members. We developed an ethyl derivative of an existing small-molecule inhibitor, I-BET/JQ1, and showed that it binds leucine/alanine mutant bromodomains with nanomolar affinity and achieves up to 540-fold selectivity relative to wild-type bromodomains. Cell culture studies showed that blockade of the first bromodomain alone is sufficient to displace a specific BET protein, Brd4, from chromatin. Expansion of this approach could help identify the individual roles of single BET proteins in human physiology and disease.

PubMed: 25323695
DOI: 10.1126/science.1249830

実験手法

X-RAY DIFFRACTION (1.5 Å)