5E9L

Crystal Structure of BAZ2B bromodomain in complex with fragment F103

5E9L の概要

• エントリーDOI: 10.2210/pdb5e9l/pdb
• 関連するPDBエントリー: 5DYU 5DYX 5E9I 5E9K
• 分子名称: Bromodomain adjacent to zinc finger domain protein 2B, 1H-indazol-6-amine (3 entities in total)
• 機能のキーワード: four helical bundle, transcription
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Nucleus : Q9UIF8
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 13664.73

構造登録者

Lolli, G.,Caflisch, A. (登録日: 2015-10-15, 公開日: 2016-03-16, 最終更新日: 2024-01-10)

主引用文献

Lolli, G.,Caflisch, A.
High-Throughput Fragment Docking into the BAZ2B Bromodomain: Efficient in Silico Screening for X-Ray Crystallography.
Acs Chem.Biol., 11:800-807, 2016

PubMed Abstract: Bromodomains are protein modules that bind to acetylated lysine side chains in histones and other proteins. The bromodomain adjacent to zinc finger domain protein 2B (BAZ2B) has been reported to be poorly druggable. Here, we screened an in-house library of 350 fragments by automatic docking to the BAZ2B bromodomain. The top 12 fragments according to the predicted binding energy were selected for experiments of soaking into apo crystals of BAZ2B which yielded the structure of the complex for four of them, which is a hit rate of 33%. Additional crystal structures were solved for BAZ2B and two scaffolds identified by analogy. For three topologically similar fragments, the crystal structures reveal binding modes with different penetration, i.e., with zero, one, and two water molecules, respectively, located between the fragment and the side chain of a conserved tyrosine (Tyr1901) in the bottom of the acetyl lysine pocket of BAZ2B. Furthermore, a remarkable stereoselectivity of the acetyl lysine pocket emerges from the crystal structures of the bromodomains of BAZ2B and SMARCA4 in complex with the chiral diol MPD (2-methyl-2,4-pentanediol).

PubMed: 26942307
DOI: 10.1021/acschembio.5b00914

実験手法

X-RAY DIFFRACTION (1.9 Å)