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dc.contributor.authorShin, David S.
dc.contributor.authorDiDonato, Michael
dc.contributor.authorBarondeau, David P.
dc.contributor.authorHura, Greg L.
dc.contributor.authorHitomi, Chiharu
dc.contributor.authorBerglund, J. Andrew
dc.contributor.authorGetzoff, Elizabeth D.
dc.contributor.authorCary, S. Craig
dc.contributor.authorTainer, John A.
dc.coverage.spatialEnglanden_NZ
dc.date.accessioned2010-05-04T00:10:53Z
dc.date.available2010-05-04T00:10:53Z
dc.date.issued2009
dc.identifier.citationShin, D. S., DiDonato, M., Barondeau, D. P., Hura, G. L., Hitomi, C., ..., Tainer, J. A. (2009). Superoxide Dismutase from the Eukaryotic Thermophile Alvinella pompejana: Structures, Stability, Mechanism, and Insights into Amyotrophic Lateral Sclerosis. Journal of Molecular Biology, 385(5-6), 1534-1555.en
dc.identifier.urihttps://hdl.handle.net/10289/3851
dc.description.abstractProkaryotic thermophiles supply stable human protein homologs for structural biology; yet, eukaryotic thermophiles would provide more similar macromolecules plus those missing in microbes. Alvinella pompejana is a deep-sea hydrothermal-vent worm that has been found in temperatures averaging as high as 68 °C, with spikes up to 84 °C. Here, we used Cu,Zn superoxide dismutase (SOD) to test if this eukaryotic thermophile can provide insights into macromolecular mechanisms and stability by supplying better stable mammalian homologs for structural biology and other biophysical characterizations than those from prokaryotic thermophiles. Identification, cloning, characterization, X-ray scattering (small-angle X-ray scattering, SAXS), and crystal structure determinations show that A. pompejana SOD (ApSOD) is superstable, homologous, and informative. SAXS solution analyses identify the human-like ApSOD dimer. The crystal structure shows the active site at 0.99 Å resolution plus anchoring interaction motifs in loops and termini accounting for enhanced stability of ApSOD versus human SOD. Such stabilizing features may reduce movements that promote inappropriate intermolecular interactions, such as amyloid-like filaments found in SOD mutants causing the neurodegenerative disease familial amyotrophic lateral sclerosis or Lou Gehrig's disease. ApSOD further provides the structure of a long-sought SOD product complex at 1.35 Å resolution, suggesting a unified inner-sphere mechanism for catalysis involving metal ion movement. Notably, this proposed mechanism resolves apparent paradoxes regarding electron transfer. These results extend knowledge of SOD stability and catalysis and suggest that the eukaryote A. pompejana provides macromolecules highly similar to those from humans, but with enhanced stability more suitable for scientific and medicalen
dc.language.isoen
dc.publisherElsevieren_NZ
dc.subjectthermophileen
dc.subjectthermostable proteinsen
dc.subjectsuperoxide dismutaseen
dc.subjectamyotrophic lateralen
dc.subjectamyloid filamentsen
dc.titleSuperoxide Dismutase from the Eukaryotic Thermophile Alvinella pompejana: Structures, Stability, Mechanism, and Insights into Amyotrophic Lateral Sclerosisen
dc.typeJournal Articleen
dc.identifier.doi10.1016/j.jmb.2008.11.031en
dc.relation.isPartOfJournal of Molecular Biologyen_NZ
pubs.begin-page1534en_NZ
pubs.elements-id33765
pubs.end-page1555en_NZ
pubs.issue5en_NZ
pubs.volume385en_NZ


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