Scheme 1.

Proposed reaction cycle for Arr based on the mechanism of other Mo-bisPGD proteins. The reduced form of Arr contains Mo(IV) coordinated by two PGD cofactors and a cysteine side chain (Top Left). Upon binding to the protein, arsenate coordinates to the Mo atom (Top Right). An oxygen atom from arsenate is transferred to the Mo atom to form Mo(VI) and arsenite (Bottom Right). The cofactor is regenerated by sequential one-electron reductions, first to the EPR active Mo(V) species (Bottom Left) and then to Mo(IV) (Top Left). Although we have illustrated it here as H₂AsO₄⁻, the protonation state of bound arsenate is unknown and might instead be HAsO₄²⁻. Also unknown is whether the final water dissociates as illustrated (Bottom Left to Top Left) or if is displaced when arsenate binds (Top Left to Top Right).