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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7
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pubmed:dateCreated |
2008-9-23
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pubmed:abstractText |
Neurodegeneration observed in Alzheimer disease (AD) is believed to be related to the toxicity from reactive oxygen species (ROS) produced in the brain by the amyloid-beta (Abeta) protein bound primarily to copper ions. The evidence for an oxidative stress role of Abeta-Cu redox chemistry is still incomplete. Details of the copper binding site in Abeta may be critical to the etiology of AD. Here we present the structure determined by combining x-ray absorption spectroscopy (XAS) and density functional theory analysis of Abeta peptides complexed with Cu(2+) in solution under a range of buffer conditions. Phosphate-buffered saline buffer salt (NaCl) concentration does not affect the high-affinity copper binding mode but alters the second coordination sphere. The XAS spectra for truncated and full-length Abeta-Cu(2+) peptides are similar. The novel distorted six-coordinated (3N3O) geometry around copper in the Abeta-Cu(2+) complexes include three histidines: glutamic, or/and aspartic acid, and axial water. The structure of the high-affinity Cu(2+) binding site is consistent with the hypothesis that the redox activity of the metal ion bound to Abeta can lead to the formation of dityrosine-linked dimers found in AD.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/18599641-10589538,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18599641-10841784,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/18599641-18072760,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18599641-18234670,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18599641-18297675,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/18599641-9334223
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1542-0086
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
95
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3447-56
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:18599641-Absorption,
pubmed-meshheading:18599641-Alzheimer Disease,
pubmed-meshheading:18599641-Amyloid beta-Peptides,
pubmed-meshheading:18599641-Binding Sites,
pubmed-meshheading:18599641-Buffers,
pubmed-meshheading:18599641-Copper,
pubmed-meshheading:18599641-Humans,
pubmed-meshheading:18599641-Models, Molecular,
pubmed-meshheading:18599641-Oxidation-Reduction,
pubmed-meshheading:18599641-Protein Binding,
pubmed-meshheading:18599641-Protein Conformation,
pubmed-meshheading:18599641-Quantum Theory,
pubmed-meshheading:18599641-Temperature,
pubmed-meshheading:18599641-X-Rays
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pubmed:year |
2008
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pubmed:articleTitle |
The structure of the amyloid-beta peptide high-affinity copper II binding site in Alzheimer disease.
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pubmed:affiliation |
Commonwealth Scientific Industrial Research Organization Molecular and Health Technologies, and Preventative Health Flagship, Parkville, Victoria 3052, Australia. victor.streltsov@csiro.au
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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