Proton distribution in one-electron reduced thioredoxin modulated by aspartate 30: A QM/MM study

Thioredoxin controls the intracellular redox potential through a disulfide/dithiol couple. In conditions of oxidative stress this protein functions by one-electron exchange in which there is formation of the disulfide radical anion. The protonation of this radical is of special importance since it commands the SS bond break leading to the oxidizing thiyl radical. We have studied this reaction by QM/MM procedures. We show that the localization of the proton depends on the protonation state of the residue Asp30. Thus it provides an explanation to the modulation of the redox activity of the protein by the Asp30 residue.