title: Flavonoids as promoters of the (pseudo-)halogenating activity of lactoperoxidase and myeloperoxidase.
abstract: In this study several flavonoids were tested for their potential to regenerate the (pseudo-)halogenating activity (hypothiocyanite formation) of the heme peroxidases lactoperoxidase (LPO) and myeloperoxidase (MPO) after hydrogen peroxide-mediated enzyme inactivation. Several flavonoid subclasses with varying hydroxylation patterns (especially of the flavonoid B-ring) were examined in order to identify structural properties of efficient enzyme regenerators. Kinetic parameters and second-order rate constants were determined. A 3',4'-dihydroxylated B-ring together with C-ring saturation and hydroxylation were found to be important structural elements, which strongly influence the flavonoid binding and oxidizability by the LPO/MPO redox intermediates Compounds I and II. In combination with docking studies these results allow an understanding of the differences between flavonoids that promote the hypothiocyanite production by LPO and MPO and those that inhibit this enzymatic reaction.
authors.affiliation: Institute for Medical Physics and Biophysics, Medical Faculty, University of Leipzig, Härtelstraße 16-18, 04107 Leipzig, Germany. Electronic address: jana.gau@medizin.uni-leipzig.de.
authors.forename: Jana
authors.initials: J
authors.lastname: Gau
authors.affiliation: Department of Chemistry, Division of Biochemistry, University of Natural Resources and Life Sciences (BOKU) Vienna, Muthgasse 18, 1190 Vienna, Austria. Electronic address: paul.furtmueller@boku.ac.at.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Furtmüller
authors.affiliation: Department of Chemistry, Division of Biochemistry, University of Natural Resources and Life Sciences (BOKU) Vienna, Muthgasse 18, 1190 Vienna, Austria. Electronic address: christian.obinger@boku.ac.at.
authors.forename: Christian
authors.initials: C
authors.lastname: Obinger
authors.affiliation: Laboratory of Structure and Function of Biological Membranes, Université Libre de Bruxelles, Boulevard du Triomphe, 1050 Brussels, Belgium. Electronic address: mprevost@ulb.ac.be.
authors.forename: Martine
authors.initials: M
authors.lastname: Prévost
authors.affiliation: Laboratory of Pharmaceutical Organic Chemistry, Institute of Pharmacy, Université Libre de Bruxelles, Boulevard du Triomphe, 1050 Brussels, Belgium. Electronic address: Pierre.Van.Antwerpen@ulb.ac.be.
authors.forename: Pierre
authors.initials: P
authors.lastname: Van Antwerpen
authors.affiliation: Institute for Medical Physics and Biophysics, Medical Faculty, University of Leipzig, Härtelstraße 16-18, 04107 Leipzig, Germany. Electronic address: juergen.arnhold@medizin.uni-leipzig.de.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Arnhold
authors.affiliation: Institute for Medical Physics and Biophysics, Medical Faculty, University of Leipzig, Härtelstraße 16-18, 04107 Leipzig, Germany. Electronic address: joerg.flemmig@medizin.uni-leipzig.de.
authors.forename: Jörg
authors.initials: J
authors.lastname: Flemmig
mesh_terms: D000818:Animals; D055162:Biocatalysis; D020134:Catalytic Domain; D002417:Cattle; D005419:Flavonoids / Q000737:chemistry*; D054879:Halogenation; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry; D007700:Kinetics; D007784:Lactoperoxidase / Q000737:chemistry*; D062105:Molecular Docking Simulation; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000737:chemistry*; D011485:Protein Binding
chemical_list: D005419:Flavonoids; D006861:Hydrogen Peroxide; D007784:Lactoperoxidase; D009195:Peroxidase
keywords: Flavonoids; Hypothiocyanite; Inflammation; Lactoperoxidase; Myeloperoxidase; Polyphenols