3MO5

Human G9a-like (GLP, also known as EHMT1) in complex with inhibitor E72

3MO5 の概要

• エントリーDOI: 10.2210/pdb3mo5/pdb
• 関連するPDBエントリー: 3FPD 3MO0 3MO2
• 分子名称: Histone-lysine N-methyltransferase, H3 lysine-9 specific 5, ZINC ION, 7-[(5-aminopentyl)oxy]-N~4~-[1-(5-aminopentyl)piperidin-4-yl]-N~2~-[3-(dimethylamino)propyl]-6-methoxyquinazoline-2,4-diamine, ... (5 entities in total)
• 機能のキーワード: epigenetics, histone lysine methylation, enzymatic inhibition, lysine mimics, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: Q9H9B1
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 135315.35

構造登録者

Chang, Y.,Horton, J.R.,Cheng, X. (登録日: 2010-04-22, 公開日: 2010-06-30, 最終更新日: 2023-09-06)

主引用文献

Chang, Y.,Ganesh, T.,Horton, J.R.,Spannhoff, A.,Liu, J.,Sun, A.,Zhang, X.,Bedford, M.T.,Shinkai, Y.,Snyder, J.P.,Cheng, X.
Adding a lysine mimic in the design of potent inhibitors of histone lysine methyltransferases.
J.Mol.Biol., 400:1-7, 2010

PubMed Abstract: Dynamic histone lysine methylation involves the activities of modifying enzymes (writers), enzymes removing modifications (erasers), and readers of the histone code. One common feature of these activities is the recognition of lysines in methylated and unmethylated states, whether they are substrates, reaction products, or binding partners. We applied the concept of adding a lysine mimic to an established inhibitor (BIX-01294) of histone H3 lysine 9 methyltransferases G9a and G9a-like protein by including a 5-aminopentyloxy moiety, which is inserted into the target lysine-binding channel and becomes methylated by G9a-like protein, albeit slowly. The compound enhances its potency in vitro and reduces cell toxicity in vivo. We suggest that adding a lysine or methyl-lysine mimic should be considered in the design of small-molecule inhibitors for other methyl-lysine writers, erasers, and readers.

PubMed: 20434463
DOI: 10.1016/j.jmb.2010.04.048

実験手法

X-RAY DIFFRACTION (2.14 Å)