4QB3

Crystal structure of the first bromodomain of human BRD4 in complex with Olinone

4QB3 の概要

• エントリーDOI: 10.2210/pdb4qb3/pdb
• 分子名称: Bromodomain-containing protein 4, N-[4-(1-oxo-1,2,3,4-tetrahydro-5H-pyrido[4,3-b]indol-5-yl)butyl]acetamide, 1,2-ETHANEDIOL, ... (4 entities in total)
• 機能のキーワード: bromodomain, transcription factor, acetyl-lysine binding, transcription-transcription inhibitor complex, transcription/transcription inhibitor
• 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: 1
• 化学式量合計: 15460.82

構造登録者

Plotnikov, A.N.,Joshua, J.,Zhou, M.-M. (登録日: 2014-05-06, 公開日: 2015-04-22, 最終更新日: 2023-09-20)

主引用文献

Gacias, M.,Gerona-Navarro, G.,Plotnikov, A.N.,Zhang, G.,Zeng, L.,Kaur, J.,Moy, G.,Rusinova, E.,Rodriguez, Y.,Matikainen, B.,Vincek, A.,Joshua, J.,Casaccia, P.,Zhou, M.M.
Selective chemical modulation of gene transcription favors oligodendrocyte lineage progression.
Chem.Biol., 21:841-854, 2014

PubMed Abstract: Lysine acetylation regulates gene expression through modulating protein-protein interactions in chromatin. Chemical inhibition of acetyl-lysine binding bromodomains of the major chromatin regulators BET (bromodomain and extraterminal domain) proteins has been shown to effectively block cell proliferation in cancer and inflammation. However, whether selective inhibition of individual BET bromodomains has distinctive functional consequences remains only partially understood. In this study, we show that selective chemical inhibition of the first bromodomain of BET proteins using our small-molecule inhibitor, Olinone, accelerated the progression of mouse primary oligodendrocyte progenitors toward differentiation, whereas inhibition of both bromodomains of BET proteins hindered differentiation. This effect was target specific, as it was not detected in cells treated with inactive analogs and independent of any effect on proliferation. Therefore, selective chemical modulation of individual bromodomains, rather than use of broad-based inhibitors, may enhance regenerative strategies in disorders characterized by myelin loss such as aging and neurodegeneration.

PubMed: 24954007
DOI: 10.1016/j.chembiol.2014.05.009

実験手法

X-RAY DIFFRACTION (0.94 Å)