Thiol-disulfide exchange is a chemical reaction in which a thiolate group $\backslash mathrm\{S\}^\{-\}$ attacks a sulfur | atom of a disulfide bond -S-S-. The old disulfide bond is broken, and a new disulfide bond forms between the attacking thiolate the attacked sulfur atom. The unattacked sulfur atom is released as a new thiolate, carrying away the negative charge.

The transition state of the reaction is a linear arrangement of the three sulfur atoms, in which the charge of the attacking thiolate is shared equally. Thiol-disulfide exchange is inhibited at low pH (typically, below 8) since the deprotonated thiolate form $\backslash mathrm\{S\}^\{-\}$ is disfavored relative to the protonated thiol form -SH, which is unreactive. (The pKa of a typical thiol group is roughly 8.3.)

Thiol-disulfide exchange is the principal reaction by which disulfide bonds are formed in a protein. Thiol-disulfide exchange can occur within a protein, when one of its free thiolate groups (from a cysteine residue) attacks one of its disulfide bonds. This process of disulfide rearrangement within a protein is known as disulfide shuffling, and does not change the number of disulfide bonds within a protein, merely their location (i.e., which cysteines are bonded). Disulfide reshuffling is generally much faster than oxidation/reduction reactions, which change the number of disulfide bonds within a protein.

References

Gilbert HF. (1990) "Molecular and Cellular Aspects of Thiol-Disulfide Exchange", Advances in Enzymology, 63, 69-172.

Gilbert HF. (1995) "Thiol/disulfide exchange equilibria and disulfide bond stability", Methods in Enzymology, 251, 8-28.

Chemical reactions