SOD2 uses cyclic proton-coupled electron transfer reactions to convert superoxide (O) into either oxygen (O) or hydrogen peroxide (HO), depending on the oxidation state of the manganese metal and the protonation status of the active site.
Mn + O ↔ Mn + O
Mn + O + 2H ↔ Mn + HO
The protons of the active site have been directly visualized and revealed that SOD2 utilizes proton transfers between a glutamine residue and a Mn-bound solvent molecule in concert with its electron transfers. During the Mn to Mn redox reaction, Gln143 donates an amide proton to hydroxide bound to the Mn and forms an amide anion. The amide anion is stabilized by short-strong hydrogen bonds (SSHBs) with the Mn-bound solvent and the nearby Trp123 residue. For the Mn to Mn redox reaction, the proton is donated back to the glutamine to reform the neutral amide state. The fast and efficient PCET catalysis of SOD2 is explained by the use of a proton that is always present and never lost to bulk solvent.