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 A. OHP oxidation results in the disruption of the Y36'-C22-Y47' interaction network and dissection of helix alpha5, which then allows the 135 degrees rotation and 8.2 A translation of C127', formation of the C22-C127' disulphide bond, and alpha6-alpha6' 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.
Newberry
Kate J
KJ
Department of Biochemistry and Molecular Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030-4009, USA.
Fuangthong
Mayuree
M
Panmanee
Warunya
W
Mongkolsuk
Skorn
S
Brennan
Richard G
RG
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics*; D018360:Crystallography, X-Ray; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D017433:Protein Structure, Secondary; D053038:Quorum Sensing / Q000187:drug effects; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics*; D055672:Static Electricity; D013329:Structure-Activity Relationship; D013379:Substrate Specificity / Q000187:drug effects; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics*; D014443:Tyrosine / Q000378:metabolism; D016959:Xanthomonas campestris / Q000187:drug effects / Q000235:genetics*
D001426:Bacterial Proteins; D050505:Mutant Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C122138:peroxide repressor proteins; D014443:Tyrosine; D006861:Hydrogen Peroxide