Under high hydroperoxide concentrations, C\({}_{\rm P}\) can undergo further oxidation generating hyperoxidized species (C\({}_{\rm P}\)-SO\({}_{2}\)H or C\({}_{\rm P}\)-SO\({}_{3}\)H) rather than forming the disulfide bond, inactivating Prx turnover by Trx [27; 28]. However, the enzyme sulfiredoxin (Srx) can reduce C\({}_{\rm P}\)-SO\({}_{2}\)H to C\({}_{\rm P}\)-SOH in a process dependent on ATP hydrolysis for typical 2-Cys Prx [27; 28]. Hyperoxidized 2-Cys Prx are frequently associated with a molecular chaperone (holidase) function and may impact signaling pathways, like cell growth and circadian rhythm [29; 30; 31; 32]. In addition to C\({}_{\rm P}\) hyperoxidation, high temperatures can also confer chaperone function to these enzymes [33; 34; 35; 36]. A remarkable feature of 2-Cys Prx is the structural rearrangement that are triggered by C\({}_{\rm P}\) oxidation. Reduced 2-Cys Prx enzymes (C\({}_{\rm P}\)-S\({}^{-}\)) are stabilized as decamers [(\(\alpha_{2}\))\({}_{5}\)] and can assume the so called fully folded (FF) state (Figure 1A), in which C\({}_{\rm P}\) is located in the first turn of an \(\alpha\)-helix near to N-terminal region of the protein and far away from C\({}_{\rm R}\) (10-16 A), which is located in the C-terminus of these enzymes. Upon oxidation, partial unfolding of the \(\alpha\)-helix containing C\({}_{\rm P}\)-SOH (the so-called locally unfolded = LU state) allows its approximation to C\({}_{\rm R}\) with the consequent intermolecular disulfide bond formation [37]. In the disulfide form, the 2-Cys Prx decamers tend to dissociate into low molecular weight (LMW) species, mainly dimers [38; 39; 40] (Figure 1B). Moreover, when C\({}_{\rm P}\) is hyperoxidized or when subjected to heat shock, 2-Cys Prx can switch from decamers to higher molecular weight (HMW) species [32; 33; 35; 41; 42] (Figure 1C). Therefore, two reversible structural switches (FF-LU and decamers dissociation) are inter-connected and the stabilities of distinct conformers are influenced by thermal and/or redox factors. The transitions and stability of distinct oligomers also rely in structural peculiarities of these enzymes. In the 2-Cys Prx from _Escherichia coli_ (EcAhpC) mutations close to the C-terminal region precludes the decamer formation [43]. Factors as pH, ionic strength, and protein concentration can influence directly the quaternary state of 2-CysPrx, indicating that the oligomeric rearrangements are directly related to specialized functions of these enzymes in different organisms and cell compartments [39; 44; 45; 46; 47]. In that regard, we have shown that the presence of Thr or Ser in the catalytic triad influences the stabilities of distinct oligomeric states that 2-Cys Prx can assume [3]. Yeast Isa1 and Isa2 contain Thr or Ser in the active site, respectively. Both enzymes are decamers in the reduced state, but Isa1 is mainly a dimer when oxidized and some are intermediate species (e.g., tetramers), while Tsa2 remains as decamer even after oxidation [3]. In addition, the mutation of catalytic Thr to Ser stabilizes Tsa1 in the decameric form even when oxidized [3]. The substitution of catalytic triad Thr to Ser also stabilizes typical 2-Cys Prx from _Salmonella typhimurium_ and _Enterococcus faecalis_ as decamers [48; 49]. Here, we described that the presence of Thr and Ser in the active site also affected the sensibility of 2-Cys Prx to hyperoxidation. Previously, other structural features were described to confer sensibility of C\({}_{\rm P}\) to hyperoxidation, namely a GGLG motif (close to the active site) and a YF motif (found in a \(\alpha\)-helix in the C-terminal portion) that are present almost uniquely in eukaryotic enzymes [40]. Posteriorly, the presence of the motif A (D-X\({}_{8}\)-N/G-X\({}_{10}\)-H-X\({}_{27}\)-S/G) and of the motif B (T-X\({}_{3}\)-S/T) were associated with increased resistance of 2-Cys Prx to hyperoxidation [50].