3ZMT

LSD1-CoREST in complex with PRSFLV peptide

3ZMT の概要

• エントリーDOI: 10.2210/pdb3zmt/pdb
• 関連するPDBエントリー: 3ZMS 3ZMU 3ZMV 3ZMZ 3ZN0 3ZN1
• 分子名称: LYSINE-SPECIFIC HISTONE DEMETHYLASE 1A, REST COREPRESSOR 1, PEPTIDE, ... (4 entities in total)
• 機能のキーワード: oxidoreductase-peptide complex, demethylase, transcription factor, chromatin, oxidoreductase/peptide
• 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: 149452.61

構造登録者

Tortorici, M.,Borrello, M.T.,Tardugno, M.,Chiarelli, L.R.,Pilotto, S.,Ciossani, G.,Vellore, N.A.,Cowan, J.,O'Connell, M.,Mai, A.,Baron, R.,Ganesan, A.,Mattevi, A. (登録日: 2013-02-12, 公開日: 2013-06-12, 最終更新日: 2023-12-20)

主引用文献

Tortorici, M.,Borrello, M.T.,Tardugno, M.,Chiarelli, L.R.,Pilotto, S.,Ciossani, G.,Vellore, N.A.,Bailey, S.G.,Cowan, J.,O'Connell, M.,Crabb, S.J.,Packham, G.K.,Mai, A.,Baron, R.,Ganesan, A.,Mattevi, A.
Protein Recognition by Small Peptide Reversible Inhibitors of the Chromatin-Modifying Lsd1/Corest Lysine Demethylase.
Acs Chem.Biol., 8:1677-, 2013

PubMed Abstract: The combinatorial assembly of protein complexes is at the heart of chromatin biology. Lysine demethylase LSD1(KDM1A)/CoREST beautifully exemplifies this concept. The active site of the enzyme tightly associates to the N-terminal domain of transcription factors of the SNAIL1 family, which therefore can competitively inhibit the binding of the N-terminal tail of the histone substrate. Our enzymatic, crystallographic, spectroscopic, and computational studies reveal that LSD1/CoREST can bind to a hexapeptide derived from the SNAIL sequence through recognition of a positively charged α-helical turn that forms upon binding to the enzyme. Variations in sequence and length of this six amino acid ligand modulate affinities enabling the same binding site to differentially interact with proteins that exert distinct biological functions. The discovered short peptide inhibitors exhibit antiproliferative activities and lay the foundation for the development of peptidomimetic small molecule inhibitors of LSD1.

PubMed: 23721412
DOI: 10.1021/CB4001926

実験手法

X-RAY DIFFRACTION (3.1 Å)