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Daouda Traore

Structural studies of the PerR protein: A metalloprotein sensor of H2O2

Published on 29 September 2008

Thesis presented September 29, 2008

Bacterial defense mechanisms towards oxidative stress are mainly based on expression of enzymes able to eleminate the reactive oxygen species such as superoxide anion, hydrogen peroxide and hydroxyl radical. The PerR protein, which belongs to the Fur family, was identified as a sensor of the hydrogen peroxide in Bacillus subtilis. PerR is a dimeric zinc protein with a regulatory metal binding site that coordinates either Fe​2+ or Mn2+. Unlike other peroxide sensors such as OxyR from Escherichia coli and Orp1-Yap1 from Saccharomyces cerevisiaie, either the structural or the biochemical characterization of PerR was not as complete.
The present work reports the structural studies of the PerR protein by X-ray crystallography and X-ray absorption spectroscopy (XAS). The resolved structures (the apoprotein, metal bound and the inactivated forms) further characterize the ​PerR protein. The DNA binding mode of PerR is also discussed.
Interestingly, while most of the peroxide sensors use redox-active cysteines to detect H2O2, the reaction of PerR with H2O2 involve two histidine residues. The oxidation of PerR is catalyzed by the regulatory metal (Fe2+) and leads to the formation of a 2-oxo-histidine residue. The four cystein residues of the protein that are involved in the coordination of the zinc ion do not participate to the hydrogen peroxide detection. The crystal structure of the oxidized protein showing a 2-oxo-histidine residue is the first example of a 2-oxo-histidine containing structure reported in the PDB.

Oxidative stress, metalloprotein, DNA/protein complex, crystallography, XAS, EXAFS, XANES

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