Identification of Cysteine Residues Involved in Disulfide Formation in the Inactivation of Glutathione Transferase P-Form by Hydrogen Peroxide

Polymorphism of the glutathione transferase subunit 3 in Sprague–Dawley rats involves a reactive cysteine residue

“…The presence of reactive cysteine residues has been reported in the Pi class GST forms [6,46]. Both GST-P (7-7) and GST 3-3 are increased in rat pre-neoplastic hepatic lesions [47], but whereas the Pi class are inactivated by H # O # through disulphide bond formation between two cysteine residues [7], this is not the case for either the asparagine\cysteine or lysine\serine forms of GST 3-3. This suggests that formation of a disulphide bond does not occur, possibly because only the residue at position 199 out of the four cysteine residues is reactive.…”

“…The forms in the Alpha class possess high glutathione peroxidase activity towards lipid hydroperoxides [4]. Conjugation reactions of the Mu-class forms are activated by active oxygen species [5], whereas the Pi class is inactivated by SH reagents and H # O # ; modification of cysteine residues being responsible [6,7]. The GST forms have been suggested to play important roles in the prevention of tissue damage by oxidative stress [3,8].…”

The role of glutathione-S-transferase in anti-cancer drug resistance

“…While the precise mechanism for the disruption of the ligand-binding interaction between these two proteins is not defined, the presence of an aggregation of GST monomers following oxidative stress implicates intermolecular disulfide bridge formation between available cysteine residues. In particular, it has been previously shown that cysteine residues at positions 14, 47, 117, and 169 of GSTp are particularly susceptible to dimerization (Shen et al, 1993). Although it was determined that residues 47 and 101 were critical to the maintenance of catalytic activity, the protein : -protein interactions between GSTp and JNK appear to be distal from, and independent of, the catalytic site of GSTp.…”

Amphibian embryo glutathione transferase: amino acid sequence and structural properties

“…Cysteine residues have been implicated in the catalytic activity of mammalian Piclass GST by a number of groups [16][17][18][19][20][21][22][23]. Chemical-modification and site-directed-mutagenesis studies showed that Cys%( in hGSTP1-1, mGSTP1-1 and rGSTP1-1 (Cys%& in pGSTP1-1) is responsible for enzyme inactivation, either by conformational changes or by preventing substrate binding [16][17][18][19][20][21][22][23]. The Cys%(, which is situated at the end of the α2 helix [10], near the GSHbinding site, may also undergo reversible oxidative inactivation by biological disulphides and thiol-group-containing compounds, forming an intra-or inter-subunit disulphide bond with Cys"!"…”

“…The Cys%(, which is situated at the end of the α2 helix [10], near the GSHbinding site, may also undergo reversible oxidative inactivation by biological disulphides and thiol-group-containing compounds, forming an intra-or inter-subunit disulphide bond with Cys"!" [20,22]. Cys%( and Cys"!…”