Fig. 3: Overview of redox post-translational modifications of cysteines

Oxidation by ROS (like H₂O₂) initially leads to sulfenylation (SOH). Sulfenylated cysteine can additionally react with ROS leading first to sulfinylation (SO₂H) and then to sulfonylation (SO₃H). While sulfonylation is so far considered irreversible, sulfinylation can be reversed through the catalytic activity of the cytoplasmic enzyme sulfiredoxin-1 (SRXN-1). Many reactions can lead to disulfide bond formation: (i) intermolecular disulfide bonds can be formed with another protein or low molecular weight thiols (glutathione for example), (ii) intramolecular disulfide bonds are often inserted into a reduced protein by disulfide exchange (via formation of mixed disulfides) with GSSG or another oxidized protein (e.g., PDI) or through reaction of the relative instable sulfenylated cysteine. Please note that reactions involving thiol groups (SH) implies the formation of thiolate (_-S^-) through deprotonation and so are strongly dependent on the local pKa