TY - JOUR
T1 - The structure of human mitochondrial manganese superoxide dismutase reveals a novel tetrameric interface of two 4-helix bundles
AU - Borgstahl, Gloria E.O.
AU - Parge, Hans E.
AU - Hickey, Michael J.
AU - Beyer, Wayne F.
AU - Hallewell, Robert A.
AU - Tainer, John A.
N1 - Funding Information:
This work was supported by National Institutes of Health grant GM39345 We thank Elizabeth Getzoff, Duncan McRee, Irwin Frido-vich, Maurice Boissinot, Michael Pique, and Brian Crane for their intellectual contributions. We thank Dagmar Ringe and Barry Stoddard for the P. ovalis FeSOD coordinates and Martha Ludwig and William Stallings for the T. thermophilus MnSOD coordinates.
PY - 1992/10/2
Y1 - 1992/10/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0026688441&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0026688441&partnerID=8YFLogxK
U2 - 10.1016/0092-8674(92)90270-M
DO - 10.1016/0092-8674(92)90270-M
M3 - Article
C2 - 1394426
AN - SCOPUS:0026688441
SN - 0092-8674
VL - 71
SP - 107
EP - 118
JO - Cell
JF - Cell
IS - 1
ER -