Fig. 7: A suggested mechanism for MnSOD product inhibition and relief.

a Product inhibition is dependent on the presence of H₂O₂ (denoted as PEO) coordinated between His30 and Tyr34 during the Mn³⁺ → Mn²⁺ redox transition. Due to the lack of experimental evidence for O₂^●− binding and uncertainty in whether it requires coordination with the Mn ion for redox catalysis, the redox reaction is instead represented by a gain of an electron. For the formation of the inhibited complex to proceed, the gain of an electron by Mn³⁺ coincides with the deprotonation of H₂O₂ by Tyr34. Note that His30 has been shown to change protonation states on both of its nitrogen atoms and could potentially extract a proton from H₂O₂ instead of Tyr34. b After the PCET, HO₂⁻ replaces the WAT1 solvent molecule to form the inhibited complex characterized by the elimination of a Gln143-WAT1 interaction while the Mn ion is in the divalent redox state. c The relief of the inhibited complex involves protonation of HO₂⁻ by Gln143 to form H₂O₂ and an ionized Gln143 and subsequent replacement of the original WAT1 position by a water molecule. d After H₂O₂ leaves the active site, the Mn²⁺SOD is formed that is characterized by an ionized Gln143 forming a SSHB with WAT1, and Tyr34, His30, and Tyr166 in the neutral states. Dashed lines represent normal hydrogen bonds, and wide dashed lines are SSHBs. The portrayal of the displayed structures and bond lengths in 2D are not representative of those seen experimentally in 3D.