3AQA

Crystal structure of the human BRD2 BD1 bromodomain in complex with a BRD2-interactive compound, BIC1

3AQA の概要

• エントリーDOI: 10.2210/pdb3aqa/pdb
• 分子名称: Bromodomain-containing protein 2, 1-[2-(1H-benzimidazol-2-ylsulfanyl)ethyl]-3-methyl-1,3-dihydro-2H-benzimidazole-2-thione, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, ... (4 entities in total)
• 機能のキーワード: structural genomics, riken structural genomics/proteomics initiative, rsgi, helical bundle, acetyl-lysine recognition, acetylated histone h4, nucleus, transcription-transcription inhibitor complex, transcription/transcription inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus (By similarity): P25440
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 46323.36

構造登録者

Umehara, T.,Nakamura, Y.,Terada, T.,Shirouzu, M.,Padmanabhan, B.,Yokoyama, S.,RIKEN Structural Genomics/Proteomics Initiative (RSGI) (登録日: 2010-10-27, 公開日: 2011-05-18, 最終更新日: 2024-10-16)

主引用文献

Ito, T.,Umehara, T.,Sasaki, K.,Nakamura, Y.,Nishino, N.,Terada, T.,Shirouzu, M.,Padmanabhan, B.,Yokoyama, S.,Ito, A.,Yoshida, M.
Real-Time Imaging of Histone H4K12-Specific Acetylation Determines the Modes of Action of Histone Deacetylase and Bromodomain Inhibitors
Chem.Biol., 18:495-507, 2011

PubMed Abstract: Histone acetylation constitutes an epigenetic mark for transcriptional regulation. Here we developed a fluorescent probe to visualize acetylation of histone H4 Lys12 (H4K12) in living cells using fluorescence resonance energy transfer (FRET) and the binding of the BRD2 bromodomain to acetylated H4K12. Using this probe designated as Histac-K12, we demonstrated that histone H4K12 acetylation is retained in mitosis and that some histone deacetylase (HDAC) inhibitors continue to inhibit cellular HDAC activity even after their removal from the culture. In addition, a small molecule that interferes with ability of the bromodomain to bind to acetylated H4K12 could be assessed using Histac-K12 in cells. Thus, Histac-K12 will serve as a powerful tool not only to understand the dynamics of H4K12-specific acetylation but also to characterize small molecules that modulate the acetylation or interaction status of histones.

PubMed: 21513886
DOI: 10.1016/j.chembiol.2011.02.009

実験手法

X-RAY DIFFRACTION (2.3 Å)