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 Mn3+ to Mn2+ 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 Mn2+ to Mn3+ 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.
