2H94

Crystal Structure and Mechanism of human Lysine-Specific Demethylase-1

2H94 の概要

• エントリーDOI: 10.2210/pdb2h94/pdb
• 分子名称: Lysine-specific histone demethylase 1, MERCURY (II) ION, FLAVIN-ADENINE DINUCLEOTIDE, ... (4 entities in total)
• 機能のキーワード: histone demethylase, oxidoreductase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus : O60341
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 75303.84

構造登録者

Stavropoulos, P.,Blobel, G.,Hoelz, A. (登録日: 2006-06-08, 公開日: 2006-07-04, 最終更新日: 2024-02-14)

主引用文献

Stavropoulos, P.,Blobel, G.,Hoelz, A.
Crystal structure and mechanism of human lysine-specific demethylase-1.
Nat.Struct.Mol.Biol., 13:626-632, 2006

PubMed Abstract: The reversible methylation of specific lysine residues in histone tails is crucial in epigenetic gene regulation. LSD1, the first known lysine-specific demethylase, selectively removes monomethyl and dimethyl, but not trimethyl modifications of Lys4 or Lys9 of histone-3. Here, we present the crystal structure of LSD1 at 2.9-A resolution. LSD1 forms a highly asymmetric, closely packed domain structure from which a long helical 'tower' domain protrudes. The active site cavity is spacious enough to accommodate several residues of the histone tail substrate, but does not appear capable of recognizing the different methylation states of the substrate lysine. This supports the hypothesis that trimethylated lysine is chemically rather than sterically discriminated. We present a biochemical analysis of LSD1 mutants that identifies crucial residues in the active site cavity and shows the importance of the SWIRM and tower domains for catalysis.

PubMed: 16799558
DOI: 10.1038/nsmb1113

実験手法

X-RAY DIFFRACTION (2.9 Å)