Peroxiredoxin System of Resists Inactivation by High Concentration of Hydrogen Peroxide-Mediated Oxidative Stress.

Most eukaryotic peroxiredoxins (Prxs) are readily inactivated by a high concentration of hydrogen peroxide (H₂O₂) during catalysis owing to their "GGLG" and "YF" motifs. However, such oxidative stress sensitive motifs were not found in the previously identified filamentous fungal Prxs. Additionally, the information on filamentous fungal Prxs is limited and fragmentary. Herein, we cloned and gained insight into Prx (An.PrxA) in the aspects of protein properties, catalysis characteristics, and especially H₂O₂ tolerability. Our results indicated that An.PrxA belongs to the newly defined family of typical 2-Cys Prxs with a marked characteristic that the "resolving" cysteine (C) is invertedly located preceding the "peroxidatic" cysteine (C) in amino acid sequences. The inverted arrangement of C and C can only be found among some yeast, bacterial, and filamentous fungal deduced Prxs. The most surprising characteristic of An.PrxA is its extraordinary ability to resist inactivation by extremely high concentrations of H₂O₂, even that approaching 600 mM. By screening the H₂O₂-inactivation effects on the components of Prx systems, including Trx, Trx reductase (TrxR), and Prx, we ultimately determined that it is the robust filamentous fungal TrxR rather than Trx and Prx that is responsible for the extreme H₂O₂ tolerence of the An.PrxA system. This is the first investigation on the effect of the electron donor partner in the H₂O₂ tolerability of the Prx system.