Model for the Exceptional Reactivity of Peroxiredoxins 2 and 3 with Hydrogen Peroxide A KINETIC AND COMPUTATIONAL STUDY

摘要: Peroxiredoxins (Prx) are thiol peroxidases that exhibit excep- tionally high reactivity toward peroxides, but the chemical basis for this is not well understood. We present strong experimental evidence two highly conserved arginine residues play a vital role in activity of human Prx2 and Prx3. Point mutation either ArgI or ArgII (in Prx3 Arg-123 Arg-146, which 3- 4 Aor 6- 7 Aaway from active site peroxidative cys- teine (Cp), respectively) each case resulted 5 orders magnitude loss reactivity. A further 2 decrease second-order rate constant was observed double mutants both isoforms, suggesting cooper- ative function these residues. Detailed ab initio theoretical calculations carried out with level G4 procedure sug- gest catalytic effects H-bond-donating functional groups to Cp sulfur reactive leaving oxygens peroxide cooperative manner. Using guanidinium cat- ion mimic group arginine, we were able locate transition structures indicate enhancements consistent our experimentally constants. Our results provide activating also involves H-bond- ing ArgII. This mechanism could explain exceptional peroxiredoxins H2O2 may have wider implications protein peroxides.