title: Small-molecule diselenides catalyze oxidative protein folding in vivo.
abstract: 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.
authors.forename: Joris
authors.initials: J
authors.lastname: Beld
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Woycechowsky
authors.forename: Donald
authors.initials: D
authors.lastname: Hilvert
mesh_terms: D002384:Catalysis; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism; D003553:Cystine / Q000737:chemistry / Q000378:metabolism; D004220:Disulfides / Q000737:chemistry / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D016566:Organoselenium Compounds / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D019704:Protein Disulfide-Isomerases / Q000235:genetics / Q000378:metabolism*; D017510:Protein Folding; D013438:Sulfhydryl Compounds / Q000378:metabolism*
chemical_list: D004220:Disulfides; D029968:Escherichia coli Proteins; D016566:Organoselenium Compounds; D013438:Sulfhydryl Compounds; D003553:Cystine; D019704:Protein Disulfide-Isomerases; C526648:dsbA protein, E coli; D003545:Cysteine