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

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

Research output: Contribution to journalArticle

381 Citations (Scopus)

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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Mitochondria
Cytotoxicity
Manganese
Medical problems
Viruses
Superoxide Dismutase
Free Radicals
Catalytic Domain
Tumor Necrosis Factor-alpha
Aging of materials
Crystal structure
Oxygen
Ligands
Enzymes
Parkinson Disease
Alzheimer Disease

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

The structure of human mitochondrial manganese superoxide dismutase reveals a novel tetrameric interface of two 4-helix bundles. / Borgstahl, Gloria E; Parge, Hans E.; Hickey, Michael J.; Beyer, Wayne F.; Hallewell, Robert A.; Tainer, John A.

In: Cell, Vol. 71, No. 1, 02.10.1992, p. 107-118.

Research output: Contribution to journalArticle

Borgstahl, Gloria E ; Parge, Hans E. ; Hickey, Michael J. ; Beyer, Wayne F. ; Hallewell, Robert A. ; Tainer, John A. / The structure of human mitochondrial manganese superoxide dismutase reveals a novel tetrameric interface of two 4-helix bundles. In: Cell. 1992 ; Vol. 71, No. 1. pp. 107-118.
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