title: Genistein inhibits activities of methylenetetrahydrofolate reductase and lactate dehydrogenase, enzymes which use NADH as a substrate.
abstract: Genistein (5, 7-dihydroxy-3- (4-hydroxyphenyl)-4H-1-benzopyran-4-one) is a natural isoflavone revealing many biological activities. Thus, it is considered as a therapeutic compound in as various disorders as cancer, infections and genetic diseases. Here, we demonstrate for the first time that genistein inhibits activities of bacterial methylenetetrahydrofolate reductase (MetF) and lactate dehydrogenase (LDH). Both enzymes use NADH as a substrate, and results of biochemical as well as molecular modeling studies with MetF suggest that genistein may interfere with binding of this dinucleotide to the enzyme. These results have implications for our understanding of biological functions of genistein and its effects on cellular metabolism.
authors.affiliation: Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Kładki 24, 80-822 Gdańsk, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Grabowski
authors.affiliation: Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Kładki 24, 80-822 Gdańsk, Poland.
authors.forename: Bogdan
authors.initials: B
authors.lastname: Banecki
authors.affiliation: Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Kładki 24, 80-822 Gdańsk, Poland.
authors.forename: Leszek
authors.initials: L
authors.lastname: Kadziński
authors.affiliation: Department of Molecular Biology, University of Gdańsk, Wita Stwosza 59, 80-308 Gdańsk, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Jakóbkiewicz-Banecka
authors.affiliation: Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Kładki 24, 80-822 Gdańsk, Poland.
authors.forename: Rajmund
authors.initials: R
authors.lastname: Kaźmierkiewicz
authors.affiliation: Laboratory of Molecular Biology (Affiliated with the University of Gdańsk), Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Wita Stwosza 59, 80-308 Gdańsk, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Gabig-Cimińska
authors.affiliation: Department of Molecular Biology, University of Gdańsk, Wita Stwosza 59, 80-308 Gdańsk, Poland.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Węgrzyn
authors.affiliation: Laboratory of Molecular Biology (Affiliated with the University of Gdańsk), Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Wita Stwosza 59, 80-308 Gdańsk, Poland.
authors.forename: Alicja
authors.initials: A
authors.lastname: Węgrzyn
authors.affiliation: Department of Neurology, Medical University of Gdańsk, Dębinki 7, 80-211 Gdańsk, Poland. Electronic address: zytabm@gumed.edu.pl.
authors.forename: Zyta
authors.initials: Z
authors.lastname: Banecka-Majkutewicz
mesh_terms: D001665:Binding Sites; D004789:Enzyme Activation; D019833:Genistein / Q000737:chemistry*; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors*; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000037:antagonists & inhibitors*; D008956:Models, Chemical; D062105:Molecular Docking Simulation; D009243:NAD / Q000737:chemistry*; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000737:chemistry; D013379:Substrate Specificity
chemical_list: D047428:Protein Kinase Inhibitors; D009243:NAD; D019833:Genistein; D007770:L-Lactate Dehydrogenase; D042965:Methylenetetrahydrofolate Reductase (NADPH2)
keywords: Genistein; Lactate dehydrogenase; Methylenetetrahydrofolate reductase; NADH