7ENV

crystal structure of NS5 in complex with the N-terminal bromodomain of BRD2 (BRD2-BD1).

7ENV の概要

• エントリーDOI: 10.2210/pdb7env/pdb
• 分子名称: Bromodomain-containing protein 2, 7-chloranyl-2-[(3-chlorophenyl)amino]pyrano[3,4-e][1,3]oxazine-4,5-dione, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: bet family, bet inhibitor, bromodomain inhibitor, brd2-bd1 inhibitor, transcription-inhibitor complex, transcription/inhibitor
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 43836.76

構造登録者

Padmanabhan, B.,Arole, A.,Deshmukh, P.,Ashok, S. (登録日: 2021-04-19, 公開日: 2022-03-09, 最終更新日: 2023-11-29)

主引用文献

Arole, A.H.,Deshmukh, P.,Sridhar, A.,Padmanabhan, B.
Structural investigation of a pyrano-1,3-oxazine derivative and the phenanthridinone core moiety against BRD2 bromodomains.
Acta Crystallogr.,Sect.F, 78:119-127, 2022

PubMed Abstract: The BET (bromodomain and extra-terminal) family of proteins recognize the acetylated histone code on chromatin and play important roles in transcriptional co-regulation. BRD2 and BRD4, which belong to the BET family, are promising drug targets for the management of chronic diseases. The discovery of new scaffold molecules, a pyrano-1,3-oxazine derivative (NSC 328111; NS5) and phenanthridinone-based derivatives (L10 and its core moiety L10a), as inhibitors of BRD2 bromodomains BD1 and BD2, respectively, has recently been reported. The compound NS5 has a significant inhibitory effect on BRD2 in glioblastoma. Here, the crystal structure of BRD2 BD2 in complex with NS5, refined to 2.0 Å resolution, is reported. Moreover, as the previously reported crystal structures of the BD1-NS5 complex and the BD2-L10a complex possess moderate electron density corresponding to the respective ligands, the crystal structures of these complexes were re-evaluated using new X-ray data. Together with biochemical studies using wild-type BRD2 BD1 and BD2 and various mutants, it is confirmed that the pyrano-1,3-oxazine and phenanthridinone derivatives are indeed potent inhibitors of BRD2 bromodomains.

PubMed: 35234137
DOI: 10.1107/S2053230X22001066

実験手法

X-RAY DIFFRACTION (2.45 Å)