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Redox manipulation of the manganese metal in human manganese superoxide dismutase for neutron diffraction
Author(s) -
Azadmanesh Jahaun,
Lutz William E.,
Weiss Kevin L.,
Coates Leighton,
Borgstahl Gloria E. O.
Publication year - 2018
Publication title -
acta crystallographica section f
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.572
H-Index - 37
ISSN - 2053-230X
DOI - 10.1107/s2053230x18011299
Subject(s) - manganese , reactive oxygen species , superoxide dismutase , redox , chemistry , hydrogen peroxide , superoxide , proton , catalysis , photochemistry , biophysics , enzyme , inorganic chemistry , biochemistry , biology , organic chemistry , physics , quantum mechanics
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.