Protein cysteine residues susceptible to S-glutathionylation (PSSG)

Protein cysteine residues susceptible to S-glutathionylation represent a specific class of reactive thiols that undergo the reversible formation of disulfide bonds with glutathione. This post-translational modification (PTM) serves as a critical mechanism for redox signaling and protects essential protein thiols from irreversible oxidative damage, such as sulfonic acid formation, during periods of oxidative stress (Gallogly & Mieyal, 2007). The susceptibility of a specific cysteine residue to S-glutathionylation is determined by its local environment, including its pKa value and accessibility within the protein structure (Ghezzi, 2005). In various disease states, including cancer and cardiovascular disorders, the balance of S-glutathionylation is often disrupted, leading to the persistent inactivation or activation of key regulatory proteins like NF-kappaB, p53, and various protein phosphatases (Dalle-Donne et al., 2009). While not a single therapeutic target, these residues are the focus of drug development strategies aimed at modulating redox homeostasis or utilizing covalent inhibitors that target specific reactive cysteines. Therapeutic interventions often involve the use of antioxidants like N-acetylcysteine or the modulation of enzymes like glutaredoxin to restore normal protein function (Mieyal et al., 2008).

Other names

Protein S-glutathionylationGlutathionylated cysteinesRedox-sensitive cysteine residuesS-glutathionylated proteins

Modulation of the cellular redox environment to alter the ratio of reduced to oxidized glutathione, or direct enzymatic deglutathionylation via glutaredoxin (Grx) to restore protein function.