6SWP

C-TERMINAL BROMODOMAIN OF HUMAN BRD2 WITH iBET-BD2 (GSK046)

これはPDB形式変換不可エントリーです。

6SWP の概要

• エントリーDOI: 10.2210/pdb6swp/pdb
• 分子名称: Bromodomain-containing protein 2, 1,2-ETHANEDIOL, 4-acetamido-3-fluoranyl-~{N}-(4-oxidanylcyclohexyl)-5-[(1~{S})-1-phenylethoxy]benzamide, ... (4 entities in total)
• 機能のキーワード: inhibitor, histone, epigenetic reader, bromodomain, brd2, bromodomain containing protein 2, antagonist, 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: 13971.07

構造登録者

Chung, C. (登録日: 2019-09-22, 公開日: 2020-04-01, 最終更新日: 2024-05-15)

主引用文献

Gilan, O.,Rioja, I.,Knezevic, K.,Bell, M.J.,Yeung, M.M.,Harker, N.R.,Lam, E.Y.N.,Chung, C.W.,Bamborough, P.,Petretich, M.,Urh, M.,Atkinson, S.J.,Bassil, A.K.,Roberts, E.J.,Vassiliadis, D.,Burr, M.L.,Preston, A.G.S.,Wellaway, C.,Werner, T.,Gray, J.R.,Michon, A.M.,Gobbetti, T.,Kumar, V.,Soden, P.E.,Haynes, A.,Vappiani, J.,Tough, D.F.,Taylor, S.,Dawson, S.J.,Bantscheff, M.,Lindon, M.,Drewes, G.,Demont, E.H.,Daniels, D.L.,Grandi, P.,Prinjha, R.K.,Dawson, M.A.
Selective targeting of BD1 and BD2 of the BET proteins in cancer and immunoinflammation.
Science, 368:387-394, 2020

PubMed Abstract: The two tandem bromodomains of the BET (bromodomain and extraterminal domain) proteins enable chromatin binding to facilitate transcription. Drugs that inhibit both bromodomains equally have shown efficacy in certain malignant and inflammatory conditions. To explore the individual functional contributions of the first (BD1) and second (BD2) bromodomains in biology and therapy, we developed selective BD1 and BD2 inhibitors. We found that steady-state gene expression primarily requires BD1, whereas the rapid increase of gene expression induced by inflammatory stimuli requires both BD1 and BD2 of all BET proteins. BD1 inhibitors phenocopied the effects of pan-BET inhibitors in cancer models, whereas BD2 inhibitors were predominantly effective in models of inflammatory and autoimmune disease. These insights into the differential requirement of BD1 and BD2 for the maintenance and induction of gene expression may guide future BET-targeted therapies.

PubMed: 32193360
DOI: 10.1126/science.aaz8455

実験手法

X-RAY DIFFRACTION (1.604 Å)