6ZS2

Crystal Structure of the bromodomain of human transcription activator BRG1 (SMARCA4) in complex with 2-(6-amino-5-(piperazin-1-yl)pyridazin-3-yl)phenol

6ZS2 の概要

• エントリーDOI: 10.2210/pdb6zs2/pdb
• 分子名称: Transcription activator BRG1, 2-(6-azanyl-5-piperazin-4-ium-1-yl-pyridazin-3-yl)phenol, 1,2-ETHANEDIOL, ... (4 entities in total)
• 機能のキーワード: bromodomain, atp-dependent helicase smarca4, brg1-associated factor 190a, baf190a, mitotic growth and transcription activator, protein brg-1, protein brahma homolog 1, snf2-beta, swi/snf-related matrix-associated actin-dependent regulator of chromatin subfamily a member 4, structural genomics consortium, sgc, transcription, gene regulation
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 29129.68

構造登録者

Preuss, F.,Joerger, A.C.,Kraemer, A.,Wanior, M.,Knapp, S.,Structural Genomics Consortium (SGC) (登録日: 2020-07-15, 公開日: 2020-10-07, 最終更新日: 2024-01-31)

主引用文献

Wanior, M.,Preuss, F.,Ni, X.,Kramer, A.,Mathea, S.,Gobel, T.,Heidenreich, D.,Simonyi, S.,Kahnt, A.S.,Joerger, A.C.,Knapp, S.
Pan-SMARCA/PB1 Bromodomain Inhibitors and Their Role in Regulating Adipogenesis.
J.Med.Chem., 63:14680-14699, 2020

PubMed Abstract: Accessibility of the human genome is modulated by the ATP-driven SWI/SNF chromatin remodeling multiprotein complexes BAF (BRG1/BRM-associated factor) and PBAF (polybromo-associated BAF factor), which involves reading of acetylated histone tails by the bromodomain-containing proteins SMARCA2 (BRM), SMARCA4 (BRG1), and polybromo-1. Dysregulation of chromatin remodeling leads to aberrant cell proliferation and differentiation. Here, we have characterized a set of potent and cell-active bromodomain inhibitors with pan-selectivity for canonical family VIII bromodomains. Targeted SWI/SNF bromodomain inhibition blocked the expression of key genes during adipogenesis, including the transcription factors PPARγ and C/EBPα, and impaired the differentiation of 3T3-L1 murine fibroblasts into adipocytes. Our data highlight the role of SWI/SNF bromodomains in adipogenesis and provide a framework for the development of SWI/SNF bromodomain inhibitors for indirect targeting of key transcription factors regulating cell differentiation.

PubMed: 33216538
DOI: 10.1021/acs.jmedchem.0c01242

実験手法

X-RAY DIFFRACTION (1.57 Å)