Get access

Studies of Inhibitor Binding to the [4Fe-4S] Cluster of Quinolinate Synthase

Authors

  • Alice Chan,

    1. Laboratoire de Chimie de Biologie des Métaux, UMR 5249, Université Joseph Fourier, Grenoble-1, CNRS-CEA 17, Rue des Martyrs, 38054 Grenoble Cedex 9 (France)
    Search for more papers by this author
  • Dr. Martin Clémancey,

    1. Laboratoire de Chimie de Biologie des Métaux, UMR 5249, Université Joseph Fourier, Grenoble-1, CNRS-CEA 17, Rue des Martyrs, 38054 Grenoble Cedex 9 (France)
    Search for more papers by this author
  • Dr. Jean-Marie Mouesca,

    1. Laboratoire de Résonances Magnétiques, SCIB (UMR-E3 CEA/UJF), INAC, CEA-Grenoble, 17 Rue des Martyrs, 38054 Grenoble Cedex 9 (France)
    Search for more papers by this author
  • Dr. Patricia Amara,

    1. Metalloproteins unit, Institut de Biologie Structurale J.-P. Ebel, CEA-CNRS Université Joseph Fourier, 41 rue Joseph Horowitz, 38027 Grenoble (France)
    Search for more papers by this author
  • Dr. Olivier Hamelin,

    1. Laboratoire de Chimie de Biologie des Métaux, UMR 5249, Université Joseph Fourier, Grenoble-1, CNRS-CEA 17, Rue des Martyrs, 38054 Grenoble Cedex 9 (France)
    Search for more papers by this author
  • Dr. Jean-Marc Latour,

    1. Laboratoire de Chimie de Biologie des Métaux, UMR 5249, Université Joseph Fourier, Grenoble-1, CNRS-CEA 17, Rue des Martyrs, 38054 Grenoble Cedex 9 (France)
    Search for more papers by this author
  • Dr. Sandrine Ollagnier de Choudens

    Corresponding author
    1. Laboratoire de Chimie de Biologie des Métaux, UMR 5249, Université Joseph Fourier, Grenoble-1, CNRS-CEA 17, Rue des Martyrs, 38054 Grenoble Cedex 9 (France)
    • Laboratoire de Chimie de Biologie des Métaux, UMR 5249, Université Joseph Fourier, Grenoble-1, CNRS-CEA 17, Rue des Martyrs, 38054 Grenoble Cedex 9 (France)
    Search for more papers by this author

  • J.M.L. acknowledges the support of the Région Rhône-Alpes through contract CIBLE 07 016335.

Abstract

original image

Stop for NadA! A [4Fe-4S] enzyme, NadA, catalyzes the formation of quinolinic acid in de novo nicotinamide adenine dinucleotide (NAD) biosynthesis. A structural analogue of an intermediate, 4,5-dithiohydroxyphthalic acid (DTHPA), has an in vivo NAD biosynthesis inhibiting activity in E. coli. The inhibitory effect can be explained by the coordination of DTHPA thiolate groups to a unique Fe site of the NadA [4Fe-4S] cluster.

Ancillary