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New roles of flavoproteins in molecular cell biology: Histone demethylase LSD1 and chromatin
Author(s) -
Forneris Federico,
Battaglioli Elena,
Mattevi Andrea,
Binda Claudia
Publication year - 2009
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2009.07142.x
Subject(s) - demethylase , biochemistry , biology , chromatin , flavoprotein , histone , histone h3 , chemistry , enzyme , gene
Lysine‐specific demethylase 1 (LSD1) is an enzyme that removes methyl groups from mono‐ and dimethylated Lys4 of histone H3, a post‐translational modification associated with gene activation. Human LSD1 was the first histone demethylase to be discovered and this enzymatic activity is conserved among eukaryotes. LSD1 has been identified in a number of chromatin‐remodeling complexes that control gene transcription and its demethylase activity has also been linked to pathological processes including tumorigenesis. The 852‐residue sequence of LSD1 comprises an amine oxidase domain which identifies a family of enzymes that catalyze the FAD‐dependent oxidation of amine substrates ranging from amino acids to aromatic neurotransmitters. Among these proteins, LSD1 is peculiar in that it acts on a protein substrate in the nuclear environment of chromatin‐remodeling complexes. This functional divergence occurred during evolution from the eubacteria to eukaryotes by acquisition of additional domains such as the SWIRM domain. The N‐terminal part of LSD1, predicted to be disordered, contains linear motifs that might represent functional sites responsible for the association of this enzyme with a variety of transcriptional protein complexes. LSD1 shares structural features with other flavin amine oxidases, including the overall fold of the amine oxidase domain region and details in the active site that are relevant for amine substrate oxidation.