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Fig. 8. The proposed mechanism for mammalian (and the DmTrxR-GCUG mutant) TrxR. Due to the low pK_a of the Sec selenol (?5.3; ref. 1), no neighboring polar Ser residue is required to facilitate formation of the disulfide-attacking selenolate (species 1 and 2) with high intrinsic nucleophilicity. The formation of the thiolate (as in species 3, see Fig. 4 in the main text) can be facilitated by a polar Ser residue (as indicated by the k_cat values in Fig. 1 in the main text), yet its absence does not significantly affect turnover with the Sec mutant forms.

1. Huber, R. E. & Criddle, R. S. (1967) Arch. Biochem. Biophys. 122, 164?173.