Nitration of tyrosine 92 mediates the activation of rat microsomal glutathione S-transferase by peroxynitrite

摘要: There is increasing evidence that protein function can be modified by nitration of tyrosine residue(s), a reaction catalyzed proteins with peroxidase activity, or occurs interaction peroxynitrite, highly reactive oxidant formed the nitric oxide superoxide. Although there are numerous reports describing loss after treatment we recently demonstrated microsomal glutathione S-transferase 1 activated rather than inactivated peroxynitrite and suggested this could attributed to residues other effects peroxynitrite. In report, nitrated peroxynitrite-treated were characterized mass spectrometry their functional significance determined. Of seven present in protein, only those at positions 92 153 Three mutants (Y92F, Y153F, Y92F, Y153F) created using site-directed mutagenesis expressed LLC-PK1 cells. Treatment fractions these cells resulted an ∼2-fold increase enzyme activity expressing wild type Y153F mutant, whereas Y92F double site mutant was unaffected. These results indicate activation mediated residue represents one few examples which gain has been associated specific residue.