In Bacillus subtilis, the transcription factor PerR is an iron dependant sensor of H2O2. The sensing mechanism relies on a selective metal catalysed oxidation of two histidine residues of the regulatory site. Here we present the first crystal structure of the active PerR protein in complex with a Mn2+ ion. In addition, X-ray absorption spectroscopy experiments were performed to characterize the corresponding iron form of the protein. Both studies reveal a penta- coordinate arrangement of the regulatory site that involves three histidines and two aspartates. One of the histidine ligand belongs to the N-terminal domain. Binding of this residue to the regulatory metal allows the protein to adopt a caliper-like conformation suited to DNA binding. Since this histidine is conserved in all PerR and a vast majority of Fur proteins, it is likely that the allosteric switch induced by the regulatory metal is general for this family of metalloregulators.
Jacquamet, L., Traore, D. A. K.
, Ferrer, J. -L., Proux, O., Testemale, D., Hazemann, J. -L., Nazarenko, E., El Ghazouani, A., Caux-Thang, C., Duarte, V., & Latour, J. -M. (2009). Structural characterization of the active form of PerR: Insights into the metal-induced activation of PerR and fur proteins for DNA binding
. Molecular Microbiology
(1), 20 - 31. https://doi.org/10.1111/j.1365-2958.2009.06753.x