Redox manipulation of the manganese metal in human manganese superoxide dismutase for neutron diffraction

Jahaun Azadmanesh, William E. Lutz, Kevin L. Weiss, Leighton Coates, Gloria E.O. Borgstahl

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Human manganese superoxide dismutase (MnSOD) is one of the most significant enzymes in preventing mitochondrial dysfunction and related diseases by combating reactive oxygen species (ROS) in the mitochondrial matrix. Mitochondria are the source of up to 90% of cellular ROS generation, and MnSOD performs its necessary bioprotective role by converting superoxide into oxygen and hydrogen peroxide. This vital catalytic function is conducted via cyclic redox reactions between the substrate and the active-site manganese using proton-coupled electron transfers. Owing to protons being difficult to detect experimentally, the series of proton transfers that compose the catalytic mechanism of MnSOD are unknown. Here, methods are described to discern the proton-based mechanism using chemical treatments to control the redox state of large perdeuterated MnSOD crystals and subsequent neutron diffraction. These methods could be applicable to other crystal systems in which proton information on the molecule in question in specific chemical states is desired.Human mitochondrial manganese superoxide dismutase (MnSOD) is a major player in combating reactive oxygen species in the human body. Methods have been found to control the redox state of the active-site metal of large perdeuterated MnSOD crystals. Neutron diffraction data from these crystals were collected to study the effect of the redox state on proton location. These methods can be applied to other crystal systems where information on the location of protons in specific chemical states is needed.

Original languageEnglish (US)
Pages (from-to)677-687
Number of pages11
JournalActa Crystallographica Section F: Structural Biology Communications
Volume74
Issue number10
DOIs
StatePublished - Oct 2018

Keywords

  • human
  • large unit cell
  • manganese superoxide dismutase
  • neutron diffraction
  • oxidation
  • perdeuteration
  • reduction

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Genetics
  • Condensed Matter Physics

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