6YB4

Crystal structure of human ATAD2 bromodomain in complex with N-(4-bromo-3-(3-methylpyrrolidin-1-yl)sulfonyl)phenyl)-2-(-4-cyclopropyl-4-methyl-2,5-dioxoimidazolidin-1-yl)acetamide

これはPDB形式変換不可エントリーです。

6YB4 の概要

• エントリーDOI: 10.2210/pdb6yb4/pdb
• 分子名称: ATPase family AAA domain-containing protein 2, SULFATE ION, 1,2-ETHANEDIOL, ... (5 entities in total)
• 機能のキーワード: inhibitor, atad2, bromodomain, epigenetics, atpase family aaa domain-containing protein 2, transcription
• 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: 16345.25

構造登録者

Chung, C. (登録日: 2020-03-15, 公開日: 2020-05-06, 最終更新日: 2024-05-15)

主引用文献

Lucas, S.C.C.,Atkinson, S.J.,Bamborough, P.,Barnett, H.,Chung, C.W.,Gordon, L.,Mitchell, D.J.,Phillipou, A.,Prinjha, R.K.,Sheppard, R.J.,Tomkinson, N.C.O.,Watson, R.J.,Demont, E.H.
Optimization of Potent ATAD2 and CECR2 Bromodomain Inhibitors with an Atypical Binding Mode.
J.Med.Chem., 63:5212-5241, 2020

PubMed Abstract: Most bromodomain inhibitors mimic the interactions of the natural acetylated lysine (KAc) histone substrate through key interactions with conserved asparagine and tyrosine residues within the binding pocket. Herein we report the optimization of a series of phenyl sulfonamides that exhibit a novel mode of binding to non-bromodomain and extra terminal domain (non-BET) bromodomains through displacement of a normally conserved network of four water molecules. Starting from an initial hit molecule, we report its divergent optimization toward the ATPase family AAA domain containing 2 (ATAD2) and cat eye syndrome chromosome region, candidate 2 (CECR2) domains. This work concludes with the identification of (GSK232), a highly selective, cellularly penetrant CECR2 inhibitor with excellent physicochemical properties.

PubMed: 32321240
DOI: 10.1021/acs.jmedchem.0c00021

実験手法

X-RAY DIFFRACTION (1.85 Å)