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 activated by the oxidation of the [2Fe-2S]. In this review, I 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 a 10-fold smaller rate constant (4.0 × 107 M−1s−1). This difference in rate constants may reflect distinct regulatory features of EcSoxR and PaSoxR. Specifically, mutagenesis studies have shown that Lysine residues―which are located close to [2Fe-2S] clusters, in EcSoxR, but are not conserved in PaSoxR―are essential for EcSoxR activation. In contrast, 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. Importantly, both O2− and RACs oxidize SoxR with the same rate constants. soxR regulon may be induced through multiple pathways, and the activation may depend on the cellular concentration of O2− and RACs.