Enzymologie moléculaire d'une sulfinyl réductase, la sulfirédoxine : Caractérisation du mécanisme catalytique

Abstract : Typical two-cysteine peroxiredoxines are involved in cell resistance against H2O2-induced oxidative stress, by reducing H2O2 in H2O. Furthermore, these enzymes take part in H2O2 signalling, which is transmitted and regulated by their redox state. The eukaryotic typical 2-Cys Prxs are subject to post-translational modification under sulfinic acid oxidation state, which inactivates have lost their peroxidase activity and thus regulates allows the passage of H2O2-dependent cellular message. Reduction of the sulfinic acid oxidation state is essential for the cell viability. Sulfiredoxin (Srx) catalyzes this reduction. These research studies demonstrated that the catalytic mechanism of Srx occurs in three steps: first, the sulfinic acid is activated as a sulfinyl phosphoryl anhydride intermediate by a direct transfer of the ?-phosphate of ATP; second, the activated sulfinic acid intermediate is reduced via attack of the catalytic Cys of Srx, which leads to formation of a thiosulfinate intermediate and; third Srx, is recycled with concomitant release of the PrxSOH product of the reaction. Two classes of Srx could be defined depending on the mechanism of Srx recycling. The class comprising yeast Srxs have one recycling Cys. This Cys attacks the thiosulfinate intermediate, resulting in PrxSOH release and formation of an oxidized Srx intermediate. This oxidized species, with an intramolecular disulfide bond, is recognized and reduced by thioredoxin. In the class comprising Srx devoid of recycling Cys, which includes the mammalian Srxs, Srx is recycled by a reducer distinct from thioredoxin, which reduces directly the thiosulfinate function.
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Xavier Roussel. Enzymologie moléculaire d'une sulfinyl réductase, la sulfirédoxine : Caractérisation du mécanisme catalytique. Sciences agricoles. Université Henri Poincaré - Nancy 1, 2009. Français. ⟨NNT : 2009NAN10082⟩. ⟨tel-01748377⟩

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