Functional Diversity of the Oxidative Stress Sensor and Transcription Factor SoxR: Mechanism of [2Fe-2S] Cluster Oxidation

The [2Fe-2S] transcription activator SoxR, a member of the MerR family, functions as a bacterial stress-response sensor. The response governed by SoxR is mediated either directly or indirectly by superoxide (O2-). In this review, we describe functional differences between Escherichia coli SoxR (EcSoxR) and Pseudomonas aeruginosa SoxR (PaSoxR). Pulse radiolysis demonstrated that the reduced form of EcSoxR reacts directly with O2- with a second-order rate constant of 5.0 × 108 M-1s-1. PaSoxR was found to undergo a similar reaction, although with 10-fold smaller rate constant (4.0 × 107 M-1s-1). This difference in rate constants reflects distinct regulatory features of EcSoxR and PaSoxR. Specifically, mutagenesis studies, have shown that Lysine residues, located close to [2Fe-2S] clusters, in EcSoxR―which are not conserved in PaSoxR―are essential for EcSoxR activation. Supporting the model of indirect activation by O2-, both EcSoxR and PaSoxR were found to react with various redox-active compounds (RACs), including viologens, phenazines, and quinones, with no apparent differences in the kinetic behavior or specificity of the two proteins.