Factors affecting redox potential and differential sensitivity of SoxR to redox-active compounds

摘要: Summary SoxR is a [2Fe-2S]-containing sensor-regulator, which activated through oxidation by redox-active compounds (RACs). SoxRs show differential sensitivity to RACs, partly due different redox potentials, such that Escherichia coli (Ec) SoxR with lower potential respond broader range of RACs than Streptomyces coelicolor (Sc) SoxR. In S. coelicolor, the do not activate ScSoxR did inhibit growth, suggesting tuned growth-inhibitory RACs. Based on sequence comparison and mutation studies, two critical amino acids around [2Fe-2S] binding site were proposed as key determinants sensitivity. ScSoxR-like (R127L/P131V) in EcSoxR changed its profile ScSoxR, whereas EcSoxR-like (L126R/V130P) caused relaxed response. accordance, potentials EcSoxRR127L/P131V ScSoxRL126R/V130P estimated be −192 ± 8 mV −273 ± 10 mV, respectively, approaching (−185 mV) (−290 mV). Molecular dynamics simulations revealed R127L P131V substitutions more electropositive environment [2Fe-2S], making it harder get oxidized. This reveals mechanism modulate redox-potential [Fe-S]-containing sensors point mutations evolve sensor achieve optimal cellular physiology.