Direct detection of coupled proton and electron transfers in human manganese superoxide dismutase
Year: 2020
Type: article
Abstract: Human manganese superoxide dismutase (MnSOD) is a critical oxidoreductase found in the mitochondria matrix. Concerted proton and electron transfers (CPETs) are used by the enzyme to rid the mitochondria of O2-, a precursor to other reactive oxygen species (ROS) that are harmful in excessive amounts. The mechanism of CPETutilizing enzymes are difficult to discern due to the inability to directly detect the protonation states of specific residues and solvent molecules involved in catalysis while controlling the redox state of the enzyme. Here, we utilize neutron diffraction of redox-controlled MnSOD crystals to yield all-atom structures of Mn3+SOD and Mn2+SOD revealing five sites of differential protonations. A novel mechanism is introduced from the direct observation of a glutamine amide-imidic acid tautomerization and three locations of low-barrier hydrogen bonds that change with the oxidation state of the metal. Quantum calculations provide insight into electronic modulation and thermodynamic properties of the observed structures.
Authors: Jahaun Azadmanesh, William Lutz, Leighton Coates, Kevin Weiss, Gloria E. O. Borgstahl
Language: English
Subfield: Inorganic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: bronze
OpenAlex ID: W3163876185