Mechanism of glutathionylation of the active site thiols of peroxiredoxin 2.

ABSTRACT: Peroxiredoxin 2 (Prdx2) undergoes ready glutathionylation, and glutaredoxin-catalyzed deglutathionylation provides an alternative mechanism to thioredoxin/thioredoxin reductase for recycling the reduced protein (Peskin et al. JBC 216, 3053, 2016). To elucidate the mechanism of glutathionylation, we have carried out kinetic studies using stopped flow and SDS PAGE plus product analysis by mass spectrometry. Kinetic modeling shows a mechanism in which exchange of Prdx2 disulfide with physiological concentrations of GSH occurs over seconds to minutes, initially at one active site to produce glutathionylated dimers linked by one disulfide. Exchange with GSH yields glutathionylation at both the peroxidatic (C_P) and resolving cysteines (C_R), the former predominating. Rate co

SUBMITTER: Peskin AV 

PROVIDER: S-EPMC12137162 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature