Human mitochondrial manganese superoxide dismutase polymorphic variant Ile58Thr reduces activity by destabilizing the tetrameric interface.

@article{Borgstahl1996HumanMM,
  title={Human mitochondrial manganese superoxide dismutase polymorphic variant Ile58Thr reduces activity by destabilizing the tetrameric interface.},
  author={Gloria E. O. Borgstahl and Hans E. Parge and Michael J. Hickey and M. J. Johnson and Maurice Boissinot and R. A. Hallewell and James R. Lepock and Diane E. Cabelli and John A. Tainer},
  journal={Biochemistry},
  year={1996},
  volume={35 14},
  pages={
          4287-97
        }
}
Human manganese superoxide dismutase (MnSOD) is a homotetrameric enzyme which protects mitochondria against oxygen-mediated free radical damage. Within each subunit, both the N-terminal helical hairpin and C-terminal alpha/beta domains contribute ligands to the catalytic manganese site. Two identical four-helix bundles, symmetrically assembled from the N-terminal helical hairpins, form a novel tetrameric interface that stabilizes the active sites. The 2.5 A crystallographic structure of the… Expand
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References

SHOWING 1-2 OF 2 REFERENCES
Involvement of O2 radicals in ‘autoimmune’ diabetes
TLDR
In vivo treatment of spontaneously diabetic NOD mice with the enzyme superoxide dismutase and catalase protects islet tissue from disease recurrence following transplantation into spontaneously diabetic mice, indicating that oxygen metabolites, specially superoxide and hydrogen peroxide, are directly involved in the pathogenesis of immunology mediated diabetes. Expand
Free radicals in biology and medicine
1. Oxygen is a toxic gas - an introductionto oxygen toxicity and reactive species 2. The chemistry of free radicals and related 'reactive species' 3. Antioxidant defences Endogenous and Diet DerivedExpand