High resolution

Module 2: Figure recovery of protein oxidation



Recovery of protein oxidation by the thioredoxin and glutaredoxin systems.

These two systems operate through protein disulphide oxidoreductases, which function to reduce the disulphide bond on the oxidized protein (red) back to the reduced thiol groups (blue). Thioredoxin (Trx) system: the active site on Trx is a -Cys-32-Gly-Pro-Cys-35- motif and it is these two cysteine residues in the reduced Trx-(SH)2 form that are responsible for reducing disulphide bonds. Upon transferring the two protons to the substrate protein, the Trx becomes oxidized to Trx-S2. Before it can operate again, the Trx-S2 must be converted back into Trx-(SH)2 by thioredoxin reductase (TrxR), which extracts reducing equivalents from the NADPH formed from the pentose cycle. Glutaredoxin (Grx) system: Grx has a -Cys-Pro-Tyr-Cys- motif, which is the active site for the oxidoreduction reaction. Glutaredoxin can act both as a dithiol–disulphide oxidoreductase and as a GSH–disulphide oxidoreductase. The latter action enables Grx to reverse mixed protein disulphides (protein-SSG not shown on the figure) formed when proteins interact with GSH. In order to continue its reducing function, the Grx-S2 or Grx-SSG must be reduced back to Grx-(SH)2 by its interaction with GSH, which is maintained in a reduced form by glutathione reductase.