Protein S-glutathionylation (PSSG) (PSSG)

Protein S-glutathionylation is a reversible post-translational modification where a glutathione molecule forms a disulfide bond with a specific cysteine residue on a target protein. This modification serves as a vital mechanism for redox signaling, allowing cells to sense and respond to changes in the oxidative environment by altering protein function, localization, or stability (Gallogly & Mieyal, 2007, PMID: 17511554). It also plays a protective role, shielding critical thiols from irreversible oxidative damage, such as the formation of sulfonic acids, during periods of oxidative stress (Gao et al., 2021, PMID: 33545284). Dysregulation of this process is implicated in a wide range of diseases, including cardiovascular disorders, neurodegeneration, and cancer, where it affects key proteins like eNOS, p53, and NF-kB (Dalle-Donne et al., 2009, PMID: 19157959). Pharmacological modulation of S-glutathionylation is an emerging therapeutic strategy, with agents like NOV-002 and glutaredoxin mimetics being explored to restore redox balance or induce targeted cell death in tumors (Townsend et al., 2009, PMID: 19147754). Because it affects a broad array of proteins, therapeutic targeting requires precision to avoid disrupting essential physiological redox signaling pathways.

Other names

Protein cysteine S-glutathionylationProtein S-glutathiolationS-glutathiolationPSSG formation

Modulation of the protein redox state through the reversible formation of mixed disulfides between glutathione and specific cysteine residues, thereby altering protein conformation and activity.