title: Flavin-Protein Complexes: Aromatic Stacking Assisted by a Hydrogen Bond.
abstract: Enzyme-catalyzed reactions often rely on a noncovalently bound cofactor whose reactivity is tuned by its immediate environment. Flavin cofactors, the most versatile catalyst encountered in biology, are often maintained within the protein throughout numbers of complex ionic and aromatic interactions. Here, we have investigated the role of π-π stacking and hydrogen bond interactions between a tyrosine and the isoalloxazine moiety of the flavin adenine dinucleotide (FAD) in an FAD-dependent RNA methyltransferase. Combining several static and time-resolved spectroscopies as well as biochemical approaches, we showed that aromatic stacking is assisted by a hydrogen bond between the phenol group and the amide of an adjacent active site loop. A mechanism of recognition and binding of the redox cofactor is proposed.
authors.affiliation: †Laboratoire de Chimie des Processus Biologiques, CNRS-UMR 8229, Collège De France, France 11 place Marcelin Berthelot, 75231 Paris Cedex 05, France.
authors.forename: Djemel
authors.initials: D
authors.lastname: Hamdane
authors.affiliation: †Laboratoire de Chimie des Processus Biologiques, CNRS-UMR 8229, Collège De France, France 11 place Marcelin Berthelot, 75231 Paris Cedex 05, France.
authors.forename: Charles
authors.initials: C
authors.lastname: Bou-Nader
authors.affiliation: ‡INSERM U779, 78 Rue du Général Leclerc, 94275 Le Kremlin-Bicêtre, France.
authors.forename: David
authors.initials: D
authors.lastname: Cornu
authors.affiliation: §Plateforme IMAGIF, Centre de Recherche de Gif, Centre National de la Recherche Scientifique, 1 avenue de le terrasse, 91191 Gif Sur Yvette, France.
authors.forename: Gaston
authors.initials: G
authors.lastname: Hui-Bon-Hoa
authors.affiliation: †Laboratoire de Chimie des Processus Biologiques, CNRS-UMR 8229, Collège De France, France 11 place Marcelin Berthelot, 75231 Paris Cedex 05, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Fontecave
mesh_terms: D000595:Amino Acid Sequence; D001412:Bacillus subtilis / Q000737:chemistry / Q000201:enzymology* / Q000378:metabolism; D020134:Catalytic Domain; D005182:Flavin-Adenine Dinucleotide / Q000737:chemistry / Q000378:metabolism*; D005415:Flavins / Q000737:chemistry* / Q000378:metabolism; D006860:Hydrogen Bonding; D008745:Methylation; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D011487:Protein Conformation; D014443:Tyrosine / Q000737:chemistry* / Q000378:metabolism; D012359:tRNA Methyltransferases / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D005415:Flavins; D005182:Flavin-Adenine Dinucleotide; D014443:Tyrosine; C008173:isoalloxazine; D012359:tRNA Methyltransferases