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dc.contributor.author Hong, Lian en_US
dc.contributor.author Carducci, Tessa M. en_US
dc.contributor.author Bush, William D. en_US
dc.contributor.author Simon, John D. en_US
dc.date.accessioned 2011-06-21T17:26:39Z
dc.date.available 2011-06-21T17:26:39Z
dc.date.issued 2010 en_US
dc.identifier.citation Hong,Lian;Carducci,Tessa M.;Bush,William D.;Dudzik,Christopher G.;Millhauser,Glenn L.;Simon,John D.. 2010. Quantification of the Binding Properties of Cu2+ to the Amyloid Beta Peptide: Coordination Spheres for Human and Rat Peptides and Implication on Cu2+-Induced Aggregation. Journal of Physical Chemistry B 114(34): 11261-11271. en_US
dc.identifier.issn 1520-6106 en_US
dc.identifier.uri http://hdl.handle.net/10161/4071
dc.description.abstract There is no consensus on the coordinating ligands for Cu2+ by A beta. However, the differences in peptide sequence between human and rat have been hypothesized to alter metal ion binding in a manner that alters Cu2+-induced aggregation of A beta. Herein, we employ isothermal titration calorimetry (ITC), circular dichroism (CD), and electron paramagnetic resonance (EPR) spectroscopy to examine the Cu2+ coordination spheres to human and rat A beta and an extensive set of A beta(16) mutants. EPR of the mutant peptides is consistent with a 3N1O binding geometry, like the native human peptide at pH 7.4. The thermodynamic data reveal an equilibrium between three coordination spheres, {NH2, O, NIm(His6), N-}, {NH2, O, N-Im(His6), N-Im(His13)}, and {NH2, O, N-Im(His6), N-Im(His14)}, for human A beta(16) but one dominant coordination for rat A beta(16), {NH2, O, N-Im(His6), N-}, at pH 7.4-6.5. ITC and CD data establish that the mutation R5G is sufficient for reproducing this difference in Cu2+ binding properties at pH 7.4. The substitution of bulky and positively charged Arg by Gly is proposed to stabilize the coordination {NH2, O-, NIm(His6), N-} that then results in one dominating coordination sphere for the case of the rat peptide. The differences in the coordination geometries for Cu2+ by the human and rat A beta are proposed to contribute to the variation in the ability of Cu2+ to induce aggregation of A beta peptides. en_US
dc.language.iso en_US en_US
dc.publisher AMER CHEMICAL SOC en_US
dc.relation.isversionof doi:10.1021/jp103272v en_US
dc.subject alzheimer a-beta en_US
dc.subject copper-binding en_US
dc.subject octarepeat domain en_US
dc.subject zinc-binding en_US
dc.subject disease en_US
dc.subject cu(ii) en_US
dc.subject protein en_US
dc.subject affinity en_US
dc.subject site en_US
dc.subject stoichiometry en_US
dc.subject chemistry, physical en_US
dc.title Quantification of the Binding Properties of Cu2+ to the Amyloid Beta Peptide: Coordination Spheres for Human and Rat Peptides and Implication on Cu2+-Induced Aggregation en_US
dc.title.alternative en_US
dc.description.version Version of Record en_US
duke.date.pubdate 2010-9-2 en_US
duke.description.endpage 11271 en_US
duke.description.issue 34 en_US
duke.description.startpage 11261 en_US
duke.description.volume 114 en_US
dc.relation.journal Journal of Physical Chemistry B en_US

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