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|dc.description.abstract||By following peroxiredoxin I (Prx I)-dependent NADPH oxidation spectrophotometrically, we observed that Prx I activity decreased gradually with time. The decay in activity was coincident with the conversion of Prx I to a more acidic species as assessed by two-dimensional gel electrophoresis. Mass spectral analysis and studies with Cys mutants determined that this shift in pI was due to selective oxidation of the catalytic site Cys51-SH to Cys51-SO2H. Thus, Cys51-SOH generated as an intermediate during catalysis appeared to undergo occasional further oxidation to Cys51-SO2H, which cannot be reversed by thioredoxin. The presence of H2O2 alone was not sufficient to cause oxidation of Cys51 to Cys51-SO2H. Rather, the presence of complete catalytic components (H2O2, thioredoxin, thioredoxin reductase, and NADPH) was necessary, indicating that such hyperoxidation occurs only when Prx I is engaged in the catalytic cycle. Likewise, hyperoxidation of Cys172/Ser172 mutant Prx I required not only H2O2, but also a catalysis-supporting thiol (dithiothreitol). Kinetic analysis of Prx I inactivation in the presence of a low steady-state level (&lt;1 μm) of H2O2 indicated that Prx I was hyperoxidized at a rate of 0.072% per turnover at 30°C. Hyperoxidation of Prx I was also detected in HeLa cells treated with H2O2.||-|
|dc.title||Inactivation of human peroxiredoxin I during catalysis as the result of the oxidation of the catalytic site cysteine to cysteine-sulfinic acid||-|
|dc.relation.journaltitle||Journal of Biological Chemistry||-|
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