Scientists reveal elusive inner workings of antioxidant enzyme with therapeutic potential

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Sumary of Scientists reveal elusive inner workings of antioxidant enzyme with therapeutic potential:

  • An enzyme called manganese superoxide dismutase, or MnSOD, uses a mechanism involving electron and proton transfers to lower ROS levels in mitochondria, thus preventing oxidative damage and maintaining cell health..
  • More than a quarter of known enzymes also rely on electron and proton transfers to facilitate cellular activities that are essential for human health..
  • Researchers from the University of Nebraska Medical Center (UNMC) and the Department of Energy’s (DOE’s) Oak Ridge National Laboratory (ORNL) have now observed the complete atomic structure of MnSOD, including its proton arrangements, with neutron scattering..
  • The work could help experts develop MnSOD-based treatments and design therapeutic drugs that mimic its antioxidant behavior..
  • “Using neutrons, we were able to see MnSOD features that were completely unexpected, and we believe this will revolutionize how people think this enzyme and other enzymes like it operate,”.
  • MnSOD works by targeting superoxide, a reactive molecule that leaks from the mitochondrial energy production process and is the chemical precursor for other harmful ROS..
  • The enzyme’s active site turns superoxide into less toxic products by using its manganese ion to move electrons to and from the reactive molecule..
  • For this biochemical reaction to work, a series of proton movements need to take place between the enzyme’s amino acids and other molecules at its active site..
  • Until now, the enzyme’s sequence of electron and proton transfers, also known as its catalytic mechanism, had not been defined at the atomic level because of challenges in tracking how protons are shuttled between molecules..
  • A fundamental understanding of this catalytic process could inform therapeutic approaches that harness this enzyme’s antioxidant abilities..
  • Thus, they can be used to study the inner workings of electron-transfer enzymes without disturbing their electronic state..
  • “Because neutrons are particles that do not interact with charge, they don’t interfere with the electronic properties of metals, which makes them an ideal probe for analyzing metal-containing enzymes, like MnSOD,”.
  • Using MaNDi, the macromolecular neutron diffractometer at ORNL’s Spallation Neutron Source (SNS), the research team was able to map out the entire atomic structure of MnSOD and track how the enzyme’s protons change when it gains or loses an electron…

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