title: MT3/QR2 melatonin binding site does not use melatonin as a substrate or a co-substrate.
abstract: Quinone reductase 2 (QR2, E.C. 1.10.99.2) is implicated in cell reactive oxygen species production. The catalytic activity of this enzyme is inhibited by 1 microM of melatonin. QR2 was identified as the third melatonin binding site (MT3). It is of major importance to understand the exact roles of melatonin and QR2 in oxidative stress. A fascinating possibility that melatonin could serve as a co-substrate or substrate of QR2 was hypothesized recently. In the current investigation, nuclear magnetic resonance studies of the QR2 catalytic reaction were performed, the results led us to conclude that, whatever the conditions, melatonin is not cleaved off to form N1-acetyl-N2-formyl-5-methoxykynurenine by a catalytically active QR2, very strongly indicating that melatonin is neither a substrate nor a co-substrate of this enzyme. Further studies are needed in order to better understand the relationship between MT3/QR2, melatonin and redox status of the cells, in order to better explain the anti-oxidant activities of melatonin at pharmacological concentrations (>1 microM).
authors.affiliation: Pharmacologie Moléculaire et Cellulaire, Institut de Recherches Servier, Croissy-sur-Seine, France. jean.boutin@fr.netgrs.com
authors.forename: Jean A
authors.initials: JA
authors.lastname: Boutin
authors.forename: Estelle
authors.initials: E
authors.lastname: Marcheteau
authors.forename: Philippe
authors.initials: P
authors.lastname: Hennig
authors.forename: Natacha
authors.initials: N
authors.lastname: Moulharat
authors.forename: Sylvie
authors.initials: S
authors.lastname: Berger
authors.forename: Philippe
authors.initials: P
authors.lastname: Delagrange
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Bouchet
authors.forename: Gilles
authors.initials: G
authors.lastname: Ferry
mesh_terms: D001665:Binding Sites; D006801:Humans; D007735:Kynuramine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D008550:Melatonin / Q000737:chemistry / Q000378:metabolism*; D019906:Nuclear Magnetic Resonance, Biomolecular; D018384:Oxidative Stress; D011808:Quinone Reductases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D044094:Receptors, Melatonin / Q000737:chemistry / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D044094:Receptors, Melatonin; D007735:Kynuramine; C041550:N-acetyl-N-formyl-5-methoxykynurenamine; C032131:N-acetyl-5-methoxy kynurenamine; D011808:Quinone Reductases; D008550:Melatonin