Structural mechanism of organic hydroperoxide induction of the transcription regulator OhrR

The Xanthomonas campestris transcription regulator OhrR contains a reactive cysteine residue (C22) that upon oxidation by organic hydroperoxides (OHPs) forms an intersubunit disulphide bond with residue C127 '. Such modification induces the expression of a peroxidase that reduces OHPs to their less toxic alcohols. Here, we describe the structures of reduced and OHP-oxidized OhrR, visualizing the structural mechanism of OHP induction. Reduced OhrR takes a canonical MarR family fold with C22 and C127 ' separated by 15.5 angstrom. OHP oxidation results in the disruption of the Y36 '-C22-Y47 ' interaction network and dissection of helix alpha 5, which then allows the 135 degrees rotation and 8.2 angstrom translation of C127 ', formation of the C22-C127 ' disulphide bond, and alpha 6-alpha 6 ' helix-swapped reconfiguration of the dimer interface. These changes result in the 28 degrees rigid body rotations of each winged helix-turn-helix motif and DNA dissociation. Similar effector-induced rigid body rotations are expected for most MarR family members.