Fig. 7.

Proposed catalytic cycle of SynFtn. (A) Apo ferroxidase center binds two Fe²⁺ ions from solution. (B) Two-electron reduction of O₂ to hydrogen peroxide leads to oxidation of a single Fe²⁺ ion, thus yielding the MVFC, and a radical on Tyr40. (C) The Tyr radical is transient and only observed in the subset of subunits where the partner subunit’s ferroxidase center is unoccupied. In the remainder, rapid electron transfer from Fe²⁺/Fe²⁺ or monomeric Fe²⁺ bound at a second ferroxidase center results in quenching of the radical. (D) Slow reaction of the MVFC with a second molecule of O₂, accompanied by transfer of a second electron from the paired ferroxidase center, results in formation of the unstable bridged diferric center observed in other ferritins and a second molecule of hydrogen peroxide. The kinetics of this process was unaltered in a Y40F variant, suggesting that Tyr40 is not required for transfer of the second electron. (E) Hydration and translocation of oxidized iron from the ferroxidase center to the internal cavity results in formation of mineral core and regeneration of apo ferroxidase centers. Overall, four ferroxidase center-bound Fe²⁺ ions are oxidized, reducing two molecules of O₂ to H₂O₂, accounting for the observed 2:1 stoichiometry.