title: Histone demethylation catalysed by LSD1 is a flavin-dependent oxidative process.
abstract: Lysine-specific histone demethylase 1 (LSD1) is a very recently discovered enzyme which specifically removes methyl groups from Lys4 of histone 3. We have addressed the functional properties of the protein demonstrating that histone demethylation involves the flavin-catalysed oxidation of the methylated lysine. The nature of the substrate that acts as the electron acceptor required to complete the catalytic cycle was investigated. LSD1 converts oxygen to hydrogen peroxide although this reactivity is not as pronounced as that of other flavin-dependent oxidases. Our findings raise the possibility that in vivo LSD1 might not necessarily function as an oxidase, but it might use alternative electron acceptors.
authors.affiliation: Dipartimento di Genetica e Microbiologia, Università di Pavia, Via Ferrata 1, 27100 Pavia, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Forneris
authors.forename: Claudia
authors.initials: C
authors.lastname: Binda
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Vanoni
authors.forename: Andrea
authors.initials: A
authors.lastname: Mattevi
authors.forename: Elena
authors.initials: E
authors.lastname: Battaglioli
mesh_terms: D002384:Catalysis; D005415:Flavins / Q000378:metabolism*; D056466:Histone Demethylases; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D010084:Oxidation-Reduction; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D005415:Flavins; D006657:Histones; D056466:Histone Demethylases; C495195:KDM1A protein, human; D010089:Oxidoreductases, N-Demethylating; D008239:Lysine