FIGURE 3.

Proposed disulfide relay mechanism of Cd-MsrA coupled to the Trx/TrxR pathway. The reaction starts with a nucleophilic attack of the Cd-MsrA Cys⁵² on the sulfoxide of l-Met-SO, which results in the formation of a sulfenic acid (-SOH) on Cys⁵², while reduced l-Met is released (step 1). Next, either Cys²⁰⁶ or Cys²¹⁵ attacks the sulfur of the -SOH on Cys⁵², causing the release of a water molecule and the formation of a Cys⁵²–Cys²⁰⁶ or Cys⁵²–Cys²¹⁵ disulfide (step 2). The second resolving Cys (either Cys²⁰⁶ or Cys²¹⁵) then attacks the sulfur of the first resolving Cys and forms a Cys²⁰⁶–Cys²¹⁵ disulfide (step 3), which is exposed to thioredoxin for regeneration (step 4).