5L3F

LSD1-CoREST1 in complex with polymyxin B

5L3F の概要

• エントリーDOI: 10.2210/pdb5l3f/pdb
• 分子名称: Lysine-specific histone demethylase 1A, REST corepressor 1, Polmyxin B, ... (4 entities in total)
• 機能のキーワード: oxidoreductase-repressor complex, lsd1, kdm1a, corest1, chromatin, epigenetic, oxidoreductase
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Nucleus : O60341 Q9UKL0
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 103531.30

構造登録者

Speranzini, V.,Rotili, D.,Ciossani, G.,Pilotto, S.,Forgione, M.,Lucidi, A.,Forneris, F.,Velankar, S.,Mai, A.,Mattevi, A. (登録日: 2016-04-10, 公開日: 2016-09-21, 最終更新日: 2024-01-10)

主引用文献

Speranzini, V.,Rotili, D.,Ciossani, G.,Pilotto, S.,Marrocco, B.,Forgione, M.,Lucidi, A.,Forneris, F.,Mehdipour, P.,Velankar, S.,Mai, A.,Mattevi, A.
Polymyxins and quinazolines are LSD1/KDM1A inhibitors with unusual structural features.
Sci Adv, 2:e1601017-e1601017, 2016

PubMed Abstract: Because of its involvement in the progression of several malignant tumors, the histone lysine-specific demethylase 1 (LSD1) has become a prominent drug target in modern medicinal chemistry research. We report on the discovery of two classes of noncovalent inhibitors displaying unique structural features. The antibiotics polymyxins bind at the entrance of the substrate cleft, where their highly charged cyclic moiety interacts with a cluster of positively charged amino acids. The same site is occupied by quinazoline-based compounds, which were found to inhibit the enzyme through a most peculiar mode because they form a pile of five to seven molecules that obstruct access to the active center. These data significantly indicate unpredictable strategies for the development of epigenetic inhibitors.

PubMed: 27626075
DOI: 10.1126/sciadv.1601017

実験手法

X-RAY DIFFRACTION (3.5 Å)