The enzyme responsible for forming disulfide bonds in proteins is:
Formation of disulfide bonds between cysteine thiol groups is critical for stability and function of many secreted and plasma membrane proteins exposed to extracellular oxidizing environment where free thiols would otherwise remain reactive. In ER lumen, protein disulfide isomerase family catalyzes oxidation, reduction and isomerization reactions essential for achieving native disulfide connectivity. Prototypical PDI contains four thioredoxin-like domains a, b, b', a' with catalytic motifs Cys-Gly-His-Cys in a and a' domains capable of forming intramolecular disulfide. Reduced substrate thiols attack oxidized PDI forming mixed disulfide intermediate, then resolved leaving substrate oxidized and PDI reduced. Reduced PDI reoxidized by flavoproteins Ero1α and Ero1β that transfer electrons to molecular oxygen generating hydrogen peroxide, detoxified by peroxiredoxin IV, GPx7 and GPx8. Isomerase activity allows correction of non-native pairings by breaking incorrect bonds and reforming correct ones. BiP acts as general Hsp70 holdase not thiol chemistry, calnexin binds monoglucosylated glycans, Sec61 conducts polypeptide chain, so assignment of disulfide formation to PDI reflects its dedicated enzymatic role central to oxidative folding capacity and extracellular proteome stability and secretion efficiency.
Ref: Ellgaard & Ruddock, EMBO Rep 6: 2005, PDI Catalyzing Disulfide Bond Formation.