Typical 2-Cys peroxiredoxins--modulation by covalent transformations and noncovalent interactions

2-Cys peroxiredoxins are peroxidases devoid of prosthetic groups that mediate in the defence against oxidative stress and the peroxide activation of signaling pathways. This dual capacity relies on the high reactivity of the conserved peroxidatic and resolving cysteines, whose modification embraces not only the usual thiol-disulfide exchange but also higher oxidation states of the sulfur atom. These changes are part of a complex system wherein the cooperation with other post-translational modifications - phosphorylation, acetylation - may function as major regulatory mechanisms of the quaternary structure. More importantly, modern proteomic approaches have identified the oxyacids at cysteine residues as novel protein targets for unsuspected post-translational modifications, such as phosphorylation that yields the unusual sulfi(o)nic-phosphoryl anhydride. In this article, we review the biochemical attributes of 2-Cys peroxiredoxins that, in combination with complementary studies of forward and reverse genetics, have generated stimulating molecular models to explain how this enzyme integrates into cell signaling in vivo.