2L85

Solution NMR structures of CBP bromodomain with small molecule of HBS

2L85 の概要

• エントリーDOI: 10.2210/pdb2l85/pdb
• 関連するPDBエントリー: 2L84
• NMR情報: BMRB: 17393
• 分子名称: CREB-binding protein, 4-[(E)-(4-hydroxyphenyl)diazenyl]benzenesulfonic acid (2 entities in total)
• 機能のキーワード: p53, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: Q92793
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 14696.83

構造登録者

Borah, J.C.,Mujtaba, S.,Karakikes, I.,Zeng, L.,Muller, M.,Patel, J.,Moshkina, N.,Morohashi, K.,Zhang, W.,Gerona-Navarro, G.,Hajjar, R.J.,Zhou, M. (登録日: 2011-01-04, 公開日: 2011-01-19, 最終更新日: 2024-05-01)

主引用文献

Borah, J.C.,Mujtaba, S.,Karakikes, I.,Zeng, L.,Muller, M.,Patel, J.,Moshkina, N.,Morohashi, K.,Zhang, W.,Gerona-Navarro, G.,Hajjar, R.J.,Zhou, M.M.
A Small Molecule Binding to the Coactivator CREB-Binding Protein Blocks Apoptosis in Cardiomyocytes.
Chem.Biol., 18:531-541, 2011

PubMed Abstract: As a master transcription factor in cellular responses to external stress, tumor suppressor p53 is tightly regulated. Excessive p53 activity during myocardial ischemia causes irreversible cellular injury and cardiomyocyte death. p53 activation is dependent on lysine acetylation by the lysine acetyltransferase and transcriptional coactivator CREB-binding protein (CBP) and on acetylation-directed CBP recruitment for p53 target gene expression. Here, we report a small molecule ischemin, developed with a structure-guided approach to inhibit the acetyl-lysine binding activity of the bromodomain of CBP. We show that ischemin alters post-translational modifications on p53 and histones, inhibits p53 interaction with CBP and transcriptional activity in cells, and prevents apoptosis in ischemic cardiomyocytes. Our study suggests small molecule modulation of acetylation-mediated interactions in gene transcription as a new approach to therapeutic interventions of human disorders such as myocardial ischemia.

PubMed: 21513889
DOI: 10.1016/j.chembiol.2010.12.021

実験手法

SOLUTION NMR