ABSTRACT
In Bacillus subtilis, the transcription factor PerR is an iron dependant sensor of H(2)O(2). 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 Mn(2+) 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.
