4XY8

Crystal Structure of the bromodomain of BRD9 in complex with a 2-amine-9H-purine ligand

4XY8 の概要

• エントリーDOI: 10.2210/pdb4xy8/pdb
• 分子名称: Bromodomain-containing protein 9, 6-(5-bromo-2-methoxyphenyl)-9H-purin-2-amine, BROMIDE ION, ... (4 entities in total)
• 機能のキーワード: bromodomain, ligand, complex, structural genomics consortium, sgc, 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: 14649.81

構造登録者

Picaud, S.,von Delft, F.,Edwards, A.M.,Arrowsmith, C.H.,Bountra, C.,Filippakopoulos, P.,Structural Genomics Consortium (SGC) (登録日: 2015-02-02, 公開日: 2015-03-11, 最終更新日: 2024-01-10)

主引用文献

Picaud, S.,Strocchia, M.,Terracciano, S.,Lauro, G.,Mendez, J.,Daniels, D.L.,Riccio, R.,Bifulco, G.,Bruno, I.,Filippakopoulos, P.
9H-Purine Scaffold Reveals Induced-Fit Pocket Plasticity of the BRD9 Bromodomain.
J.Med.Chem., 58:2718-2736, 2015

PubMed Abstract: The 2-amine-9H-purine scaffold was identified as a weak bromodomain template and was developed via iterative structure based design into a potent nanomolar ligand for the bromodomain of human BRD9 with small residual micromolar affinity toward the bromodomain of BRD4. Binding of the lead compound 11 to the bromodomain of BRD9 results in an unprecedented rearrangement of residues forming the acetyllysine recognition site, affecting plasticity of the protein in an induced-fit pocket. The compound does not exhibit any cytotoxic effect in HEK293 cells and displaces the BRD9 bromodomain from chromatin in bioluminescence proximity assays without affecting the BRD4/histone complex. The 2-amine-9H-purine scaffold represents a novel template that can be further modified to yield highly potent and selective tool compounds to interrogate the biological role of BRD9 in diverse cellular systems.

PubMed: 25703523
DOI: 10.1021/jm501893k

実験手法

X-RAY DIFFRACTION (1.7 Å)