3UVD

Crystal Structure of the bromodomain of human Transcription activator BRG1 (SMARCA4) in complex with N-Methyl-2-pyrrolidone

3UVD の概要

• エントリーDOI: 10.2210/pdb3uvd/pdb
• 関連するPDBエントリー: 3UV2 3UV4 3UV5 3UVW 3UVX 3UVY 3UW9
• 分子名称: Transcription activator BRG1, 1-methylpyrrolidin-2-one (3 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
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: P51532
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 14658.95

構造登録者

Filippakopoulos, P.,Felletar, I.,Picaud, S.,Keates, T.,Muniz, J.,Gileadi, O.,von Delft, F.,Arrowsmith, C.H.,Edwards, A.M.,Weigelt, J.,Bountra, C.,Knapp, S.,Structural Genomics Consortium (SGC) (登録日: 2011-11-29, 公開日: 2012-01-18, 最終更新日: 2023-09-13)

主引用文献

Filippakopoulos, P.,Picaud, S.,Mangos, M.,Keates, T.,Lambert, J.P.,Barsyte-Lovejoy, D.,Felletar, I.,Volkmer, R.,Muller, S.,Pawson, T.,Gingras, A.C.,Arrowsmith, C.H.,Knapp, S.
Histone recognition and large-scale structural analysis of the human bromodomain family.
Cell(Cambridge,Mass.), 149:214-231, 2012

PubMed Abstract: Bromodomains (BRDs) are protein interaction modules that specifically recognize ε-N-lysine acetylation motifs, a key event in the reading process of epigenetic marks. The 61 BRDs in the human genome cluster into eight families based on structure/sequence similarity. Here, we present 29 high-resolution crystal structures, covering all BRD families. Comprehensive crossfamily structural analysis identifies conserved and family-specific structural features that are necessary for specific acetylation-dependent substrate recognition. Screening of more than 30 representative BRDs against systematic histone-peptide arrays identifies new BRD substrates and reveals a strong influence of flanking posttranslational modifications, such as acetylation and phosphorylation, suggesting that BRDs recognize combinations of marks rather than singly acetylated sequences. We further uncovered a structural mechanism for the simultaneous binding and recognition of diverse diacetyl-containing peptides by BRD4. These data provide a foundation for structure-based drug design of specific inhibitors for this emerging target family.

PubMed: 22464331
DOI: 10.1016/j.cell.2012.02.013

実験手法

X-RAY DIFFRACTION (1.85 Å)