AI Article Synopsis
- The study utilized a QM/MM method to explore the catalytic mechanism of SOD3, focusing on electron and proton transfers involving copper and zinc ions.
- The initial step involves electron transfer from molecular oxygen to SOD3, resulting in a reduced form of the enzyme while maintaining a distorted tetrahedral structure of the copper atom.
- Protonation of His113, which connects Cu(II) and Zn(II), leads to significant conformational changes in Arg186, affecting the enzyme's ability to guide negatively charged substrates and altering proton transfer pathways.
Article Abstract
The entire enzyme catalytic mechanism including the electron and the proton transfers of the copper- and zinc-containing extracellular superoxide dismutase (SOD3) was investigated by using QM/MM method. In the first step, the electron transfer from O to SOD3 occurred without the bond formation between the donor and the acceptor and formed the triplet oxygen molecule and reduced SOD3. In the reduced SOD3, the distorted tetrahedral structure of Cu(I) atom was maintained. The reduction of Cu(II) atom induced the protonation of His113, which bridges between the Cu(II) and Zn(II) atoms in the resting state. Since the protonation of His113 broke the bond between Cu(I) and His113, three-coordinated Cu(I) was formed. Further, we suggest the binding of O formed hydrogen peroxide and the resting state after both the Cu reduction and the protonation of His113. The protonation of His113 caused the conformational change of Arg186 located at the entrance of the reactive site. The electrostatic potential surface around the reactive site showed that Arg186 plays an important role as electrostatic guidance for the negatively charged substrates only after the protonation of His113. The rotation of Arg186 switched the proton supply routes via Glu108 or Glu179 for transferring two protons from the bulk solvent.
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Article Synopsis
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