Harnessing selenocysteine reactivity for oxidative protein folding† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c4sc02379j Click here for additional data file.

Although oxidative folding of disulfide-rich proteins is often sluggish, this process can be significantly enhanced by targeted replacement of cysteines with selenocysteines. In this study, we examined the effects of a selenosulfide and native versus nonnative diselenides on the folding rates and mechanism of bovine pancreatic trypsin inhibitor. Our results show that such sulfur-to-selenium substitutions alter the distribution of key folding intermediates and enhance their rates of interconversion in a contextdependent manner.