Linked Life Data

18607649

Source:http://linkedlifedata.com/resource/pubmed/id/18607649

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2008-11-12
pubmed:abstractText
One of the many hypotheses on the pathogenesis of Alzheimer's disease is that the amyloid-beta peptide (Abeta) binds CuII and can catalytically generate H2O2, leading to oxidative damage in brain tissues. For a molecular level understanding of such catalysis it is critical to know the structure of the Abeta-CuII complex precisely. Unfortunately, no high-resolution structure is available to date and there is considerable debate over the copper coordination environment with no clear consensus on which residues are directly bound to CuII. Considering all plausible isomers of the copper-bound Abeta42 and Abeta40 using a combination of density functional theory and classical molecular dynamics methods, we report an atomic resolution structure for each possible complex. We evaluated the relative energies of these isomeric structures and surprisingly found that Abeta42 and Abeta40 display very different binding modes, suggesting that shorter peptides that are truncated at the C-terminus may not be realistic models for understanding the chemistry of the most neurotoxic peptide, Abeta42.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0949-8257
pubmed:author
pubmed:issnType
Print
pubmed:volume
13
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1197-204
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Computational study of the binding of CuII to Alzheimer's amyloid-beta peptide: do Abeta42 and Abeta40 bind copper in identical fashion?
pubmed:affiliation
Department of Chemistry and School of Informatics, Indiana University, Bloomington, IN 47405, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't