Article abstract

Nature Chemical Biology 5, 53 - 59 (2008)
Published online: 14 December 2008 | doi:10.1038/nchembio.133

Structural and functional characterization of 2-oxo-histidine in oxidized PerR protein

Daouda A K Traoré1,2,3,4, Abdelnasser El Ghazouani1,2, Lilian Jacquamet3,4,10, Franck Borel3,4, Jean-Luc Ferrer3,4, David Lascoux4,5, Jean-Luc Ravanat6,7, Michel Jaquinod8,9, Geneviève Blondin1,2, Christelle Caux-Thang1,2, Victor Duarte1,2 & Jean-Marc Latour1,2

In Bacillus subtilis, PerR is a metal-dependent sensor of hydrogen peroxide. PerR is a dimeric zinc protein with a regulatory site that coordinates either Fe2+ (PerR-Zn-Fe) or Mn2+ (PerR-Zn-Mn). Though most of the peroxide sensors use cysteines to detect H2O2, it has been shown that reaction of PerR-Zn-Fe with H2O2 leads to the oxidation of one histidine residue. Oxidation of PerR leads to the incorporation of one oxygen atom into His37 or His91. This study presents the crystal structure of the oxidized PerR protein (PerR-Zn-ox), which clearly shows a 2-oxo-histidine residue in position 37. Formation of 2-oxo-histidine is demonstrated and quantified by HPLC-MS/MS. EPR experiments indicate that PerR-Zn-H37ox retains a significant affinity for the regulatory metal, whereas PerR-Zn-H91ox shows a considerably reduced affinity for the metal ion. In spite of these major differences in terms of metal binding affinity, oxidation of His37 and/or His91 in PerR prevents DNA binding.

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  1. Commissariat à l'Energie Atomique, Institut de Recherches en Technologies et Sciences pour le Vivant, Laboratoire de Chimie et Biologie des Métaux, CEA-Grenoble, 17 avenue des Martyrs, 38054 Grenoble Cedex 9, France.
  2. Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5249, Commissariat à l'Energie Atomique, Université Joseph Fourier, CEA-Grenoble, 17 avenue des Martyrs, 38054 Grenoble Cedex 9, France.
  3. Commissariat à l'Energie Atomique, Institut de Biologie Structurale, Laboratoire de Cristallographie et Cristallogenèse des Protéines, Groupe Synchrotron, 17 avenue des Martyrs, 38054 Grenoble Cedex 9, France.
  4. Unité Mixte de Recherche 5075 Commissariat à l'Energie Atomique, Centre National de la Recherche Scientifique, Université Joseph Fourier, 41 rue Jules Horowitz, 38027 Grenoble Cedex 1, France.
  5. Commissariat à l'Energie Atomique, Institut de Biologie Structurale, Laboratoire de Spectrométrie de Masse des Protéines, 41 rue Jules Horowitz, 38027 Grenoble Cedex 1, France.
  6. Commissariat à l'Energie Atomique, Institut Nanosciences et Cryogénie, Service de Chimie Inorganique et Biologique, Lésions des Acides Nucléiques, CEA-Grenoble, 17 avenue des Martyrs, 38054 Grenoble Cedex 9, France.
  7. Laboratoire de Chimie Inorganique et Biologique, Unité Mixte de Recherche, E3 Commissariat à l'Energie Atomique, Université Joseph Fourier, 17 avenue des Martyrs, 38054 Grenoble Cedex 9, France.
  8. Commissariat à l'Energie Atomique, Institut de Recherches en Technologies et Sciences pour le Vivant, Laboratoire d'Etude de la Dynamique des Protéines, CEA-Grenoble, 17 avenue des Martyrs, 38054 Grenoble Cedex 9, France.
  9. Institut National de la Santé et de la Recherche Médicale U880, Laboratoire d'Etude de la Dynamique des Protéines, CEA-Grenoble, 17 avenue des Martyrs, 38054 Grenoble Cedex 9, France.
  10. Deceased.

Correspondence to: Victor Duarte1,2 e-mail: victor.duarte@cea.fr

Correspondence to: Jean-Marc Latour1,2 e-mail: jean-luc.ferrer@ibs.fr



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