2Y48

Crystal structure of LSD1-CoREST in complex with a N-terminal SNAIL peptide

2Y48 の概要

• エントリーDOI: 10.2210/pdb2y48/pdb
• 関連するPDBエントリー: 2COM 2H94 2IW5 2UXN 2UXX 2V1D 2X0L 2XAF 2XAG 2XAH 2XAJ 2XAQ 2XAS
• 分子名称: LYSINE-SPECIFIC DEMETHYLASE 1A, REST COREPRESSOR 1, ZINC FINGER PROTEIN SNAI1, ... (4 entities in total)
• 機能のキーワード: oxidoreductase, flavin, histone, repressor, transcription regulation, chromatin, nuclear protein
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• 細胞内の位置: Nucleus: O60341 Q9UKL0 O95863
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 104702.50

構造登録者

Baron, R.,Binda, C.,Tortorici, M.,McCammon, J.A.,Mattevi, A. (登録日: 2011-01-05, 公開日: 2011-02-16, 最終更新日: 2023-12-20)

主引用文献

Baron, R.,Binda, C.,Tortorici, M.,Mccammon, J.A.,Mattevi, A.
Molecular Mimicry and Ligand Recognition in Binding and Catalysis by the Histone Demethylase Lsd1-Corest Complex.
Structure, 19:212-, 2011

PubMed Abstract: Histone demethylases LSD1 and LSD2 (KDM1A/B) catalyze the oxidative demethylation of Lys4 of histone H3. We used molecular dynamics simulations to probe the diffusion of the oxygen substrate. Oxygen can reach the catalytic center independently from the presence of a bound histone peptide, implying that LSD1 can complete subsequent demethylation cycles without detaching from the nucleosomal particle. The simulations highlight the role of a strictly conserved active-site Lys residue providing general insight into the enzymatic mechanism of oxygen-reacting flavoenzymes. The crystal structure of LSD1-CoREST bound to a peptide of the transcription factor SNAIL1 unravels a fascinating example of molecular mimicry. The SNAIL1 N-terminal residues bind to the enzyme active-site cleft, effectively mimicking the H3 tail. This finding predicts that other members of the SNAIL/Scratch transcription factor family might associate to LSD1/2. The combination of selective histone-modifying activity with the distinct recognition mechanisms underlies the biological complexity of LSD1/2.

PubMed: 21300290
DOI: 10.1016/J.STR.2011.01.001

実験手法

X-RAY DIFFRACTION (3 Å)