The structure of human mitochondrial manganese superoxide dismutase reveals a novel tetrameric interface of two 4-helix bundles

Gloria E.O. Borgstahl, Hans E. Parge, Michael J. Hickey, Wayne F. Beyer, Robert A. Hallewell, John A. Tainer

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Abstract

The 2.2 Å resolution crystal structure of recombinant human manganese superoxide dismutase, a homotetrameric enzyme that protects mitochondria against oxygen-mediated free radical damage, has been determined. Within each subunit, both the N-terminal helical hairpin and C-terminal α β domains contribute ligands to the catalytic manganese site. Two identical 4-helix bundles, symmetrically assembled from the N-terminal helical hairpins, form novel tetrameric interfaces that stabilize the active sites. Structurally altered polymorphic variants with reduced activity, such as tetrameric interface mutant Ile-58 to Thr, may produce not only an early selective advantage, through enhanced cytotoxicity of tumor necrosis factor for virus-infected cells, but also detrimental effects from increased mitochondrial oxidative damage, contributing to degenerative conditions, including diabetes, aging, and Parkinson's and Alzheimer's diseases.

Original languageEnglish (US)
Pages (from-to)107-118
Number of pages12
JournalCell
Volume71
Issue number1
DOIs
StatePublished - Oct 2 1992

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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