Biosynthesis of selenosubtilisin: A novel way to target selenium into the active site of subtilisin

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Glutathione peroxidase (GPx, EC1.11.1.9), an important anti-oxidative selenoenzyme, can catalyze the reduction of harmful hydroperoxides with concomitant glutathione, thereby protecting cells and other biological issues against oxidative damage. It captures considerable interest in redesign of its function for either the mechanism study or the pharmacological development as an antioxidant. In order to de- velop a general strategy for specifically targeting and operating selenium in active sites of enzymes, the catalytically essential residue selenocysteine (Sec) was first successfully bioincorporated into the catalytic center of subtilisin by using an auxotrophic expression system. The studies of the catalytic activity and the steady-state kinetics demonstrated that selenosubtilisin is an excellent GPx-like bio- catalyst. In comparison with the chemically modified method, biosynthesis exhibits obvious advan- tages: Sec could be site-directly incorporated into active sites of enzymes to overcome the non-speci- ficity generated by chemical modification. This study provides an important strategy for specifically targeting and operating selenium in the active site of an enzyme. Glutathione peroxidase (GPx, EC 1.11.1.9), an important anti-oxidative selenoenzyme, can catalyze the reduction of harmful hydroperoxides with concomitant glutathione, whereby protecting cells and other biological issues against oxidative damage. It captures considerable interest in redesign of its function for either the mechanism study or the pharmacological development as an antioxidant. In order to de- velop a general strategy for specifically targeting and operating selenium in active sites of enzymes, the partially modified selenocysteine ​​(Sec) was first successfully bioincorporated into the catalytic center of subtilisin by using an auxotrophic expression system. The studies of the catalytic activity and the steady-state kinetics of that selenosubtilisin is an excellent GPx-like bio- catalyst. In comparison with the chemically modified method, biosynthesis exhibits obvious advan- tages: Sec could be site-directly incorporated into active sites of enzymes to overcome the non-speci- ficity generated by chemical modification. This study provides an important strategy for targeted targeting and operating selenium in the active site of an enzyme.
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