5ACY

N-TERMINAL BROMODOMAIN OF HUMAN BRD4 WITH 1-(2R,4S)-2-methyl-4-(phenylamino)-6-4-(piperidin-1-ylmethyl)phenyl-1,2,3,4- tetrahydroquinolin-1-yl-ethan-1-one

5ACY の概要

• エントリーDOI: 10.2210/pdb5acy/pdb
• 分子名称: BROMODOMAIN-CONTAINING PROTEIN 4, 1,2-ETHANEDIOL, 1-[(2S,4R)-2-methyl-4-(phenylamino)-6-[4-(piperidin-1-ylmethyl)phenyl]-3,4-dihydroquinolin-1(2H)-yl]ethanone, ... (4 entities in total)
• 機能のキーワード: transcription, inhibitor, histone, epigenetic reader, bromodomain, brd4, bromodomain containing protein 4, antagonist
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Nucleus: O60885
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 31292.20

構造登録者

Chung, C. (登録日: 2015-08-18, 公開日: 2015-10-07, 最終更新日: 2024-05-08)

主引用文献

Sullivan, J.M.,Badimon, A.,Schaefer, U.,Ayata, P.,Gray, J.,Chung, C.,Von Schimmelmann, M.,Zhang, F.,Garton, N.,Smithers, N.,Lewis, H.,Tarakhovsky, A.,Prinjha, R.K.,Schaefer, A.
Autism-Like Syndrome is Induced by Pharmacological Suppression of Bet Proteins in Young Mice.
J.Exp.Med., 212:1771-, 2015

PubMed Abstract: Studies investigating the causes of autism spectrum disorder (ASD) point to genetic, as well as epigenetic, mechanisms of the disease. Identification of epigenetic processes that contribute to ASD development and progression is of major importance and may lead to the development of novel therapeutic strategies. Here, we identify the bromodomain and extraterminal domain-containing proteins (BETs) as epigenetic regulators of genes involved in ASD-like behaviors in mice. We found that the pharmacological suppression of BET proteins in the brain of young mice, by the novel, highly specific, brain-permeable inhibitor I-BET858 leads to selective suppression of neuronal gene expression followed by the development of an autism-like syndrome. Many of the I-BET858-affected genes have been linked to ASD in humans, thus suggesting the key role of the BET-controlled gene network in the disorder. Our studies suggest that environmental factors controlling BET proteins or their target genes may contribute to the epigenetic mechanism of ASD.

PubMed: 26392221
DOI: 10.1084/JEM.20151271

実験手法

X-RAY DIFFRACTION (2.01 Å)