Thioredoxin domain
Thioredoxins are small disulfide-containing redox proteins that have been found in all the kingdoms of living organisms. Thioredoxin serves as a general protein disulfide oxidoreductase. It interacts with a broad range of proteins by a redox mechanism based on reversible oxidation of 2 cysteine thiol groups to a disulfide, accompanied by the transfer of 2 electrons and 2 protons. The net result is the covalent interconversion of a disulfide and a dithiol. TR-S2 + NADPH + H+ -> TR-(SH)2 + NADP+ (1) trx-S2 + TR-(SH)2 -> trx-(SH)2 + TR-S2 (2) Protein-S2 + trx-(SH)2 -> Protein-(SH)2 + trx-S2 (3) In the NADPH-dependent protein disulfide reduction, thioredoxin reductase (TR) catalyses reduction of oxidised thioredoxin (trx) by NADPH using FAD and its redox-active disulfide (steps 1 and 2). Reduced thioredoxin then directly reduces the disulfide in the substrate protein (step 3). Protein disulfide isomerase (PDI), a resident foldase of the endoplasmic reticulum, is a multi-functional protein that catalyses the formation and isomerisation of disulfide bonds during protein folding. PDI contains 2 redox active domains, near the N- and C-termini, that are similar to thioredoxin: both contribute to disulfide isomerase activity, but are functionally non-equivalent. A mutant PDI, with all 4 of the active