ACS Chem Biol. 2010 Feb 19;5(2):177-82. doi: 10.1021/cb9002688.
Prokaryotic cells normally rely on periplasmic oxidoreductases to promote oxidative protein folding. Here we show that simple diselenides can also facilitate the conversion of dithiols to disulfides in vivo, functionally replacing one such oxidoreductase, DsbA, in the oxidative folding of diverse proteins. Structurally analogous disulfides provide no detectable effect when used at concentrations that gave optimal activity with diselenides, and even at 100- to 1000-fold higher levels they show only partial activity. The low concentrations of diselenides needed to fully negate typical DsbA knockout phenotypes suggest catalysis in vivo, a property that sets these additives apart from other small molecules used in chemical biology. Supplementing growth media with cell-permeable organocatalysts provides a potentially general and operationally simple means of fine-tuning the cellular redox environment.
原核细胞通常依赖周质氧化还原酶来促进氧化蛋白质折叠。在这里，我们表明简单的二硒化物也可以在体内促进二硫键向二硫键的转化，在多种蛋白质的氧化折叠中，在功能上替代了一种氧化还原酶 DsbA。在使用二硒化物获得最佳活性的浓度下，结构类似的二硫化物没有检测到可检测的效果，即使在 100 到 1000 倍更高的水平下，它们也只显示部分活性。需要用低浓度的二硒化物来完全消除典型的 DsbA 敲除表型，这表明这些添加剂在体内具有催化作用，这一特性使它们有别于在化学生物学中使用的其他小分子。在生长培养基中补充细胞通透性有机催化剂提供了一种潜在的通用且操作简单的方法来精细调节细胞的氧化还原环境。
