Protein cysteine S-glutathionylation

Protein cysteine S-glutathionylation is a reversible post-translational modification involving the covalent attachment of a glutathione molecule to specific cysteine residues within proteins through a disulfide bond. This process serves several critical functions: "S-glutathionylation acts as a critical regulator of cellular redox balance... protecting critical thiol groups on proteins from irreversible oxidation." [1] "This reversible modification not only protects cysteine from irreversible oxidation but also causes significant structural and functional changes in the target protein..." [2] It regulates diverse biological processes including antioxidative defense, detoxification reactions, signal transduction pathways, metabolic control, cell proliferation, apoptosis regulation,[1][2] and mitochondrial function.[3] Enzymes such as glutaredoxin, glutaredoxin reductase, and various isoforms of glutathione transferases mediate its formation/removal. Dysregulation has been implicated in multiple diseases—such as cancer (where it can contribute to chemoresistance), inflammation/fibrosis (by amplifying apoptotic signals), neurodegeneration/obesity/metabolic syndrome,[3][4]—but it is not itself a druggable molecular target like an enzyme or receptor. Instead, therapeutic strategies focus on modulating upstream regulators. Because "protein cysteine S-glutathionylation" refers broadly to a chemical modification rather than an individual gene/protein product or classical drug target class (like receptor/enzyme/transporter), it should not be considered a canonical therapeutic target per se. Note: This entry describes *a type* of post-translational modification rather than an individual molecule/receptor/target suitable for structured drug discovery databases. It is therefore marked `is_incorrect: true` for use cases requiring discrete molecular targets.

Other names

S-glutathionylationProtein S-glutathionylationCysteine S-glutathionylation

Drugs or compounds may act by inhibiting or enhancing the activity of enzymes that catalyze glutathionylation/deglutathionylation, thereby indirectly affecting the extent of protein S-glutathionylation. For example, GSTπ inhibitors reduce protein glutathionylation to attenuate pathological processes like fibrosis.[4]