Selenium in Thioredoxin Reductase: Resistance to Oxidative Inactivation, Oxidation States, and Reversibility of Chemical Reactions

This study explored the role of selenium in thioredoxin reductase (TrxR) and its resistance to oxidative inactivation. Selenium, incorporated as selenocysteine (Sec) in proteins, was found to confer resistance to over-oxidation due to its greater electrophilicity compared to cysteine (Cys). This property allows for quicker resolution and prevents over-oxidation, supporting the theory that Sec was selected for its ability to impart chemical reversibility to proteins. The study also examined the use of dimedone to probe the oxidation state of Sec, finding it reacts with seleneninic and seleninic acids, questioning its utility for this purpose. Additionally, Sec-TrxR enzymes were shown to catalyze single electron reductions, likely due to a stable Sec radical intermediate. These findings highlighted the unique advantages of Sec in biological processes.