Peroxiredoxin: a case study in modelling kinetics, enzyme oligomerisation, ROS detoxification and signalling
Peroxiredoxins (Prxs) play central roles in the detoxification of reactive oxygen species. These proteins exist in multiple oligomeric forms, depending on their state of oxidation/reduction. The most common of these are dimers and decamers, with decamers predominating under reduced conditions; there is a 100-fold difference in activity between dimers and decamers. By re-analysing published data, we were able to obtain kinetic rate constants for the dimer-decamer transition and developed an approach that greatly reduces the number of species needed to model the Prx oxidation cycle. Simulation of oxidation assays showed that the dimer-decamer transition had an inhibition-like effect on peroxidase activity. Further, modelling this cycle enabled us to almost perfectly reconcile experimental and simulated responses of PRDX2 oxidation state to hydrogen peroxide insult, thus mechanistically resolving a discrepancy between experimental data and kinetic simulations. Additionally, we have demonstrated that Prx decamer dissociation occurs within a time-frame relevant to peroxidase assays and other oxidation experiments and needs to be considered when working with Prx in a laboratory.