On the Involvement of Copper Binding to the N-Terminus of the Amyloid Beta Peptide of Alzheimer's Disease : A Computational Study on Model Systems
Joint Authors
Source
International Journal of Alzheimer's Disease
Issue
Vol. 2011, Issue 2011 (31 Dec. 2011), pp.1-15, 15 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2011-12-01
Country of Publication
Egypt
No. of Pages
15
Main Subjects
Abstract EN
Density functional and second order Moller-Plesset perturbation theoretical methods, coupled with a polarizable continuum model of water, were applied to determine the structures, binding affinities, and reduction potentials of Cu(II) and Cu(I) bound to models of the Asp1, Ala2, His6, and His13His14 regions of the amyloid beta peptide of Alzheimer's disease.
The results indicate that the N-terminal Asp binds to Cu(II) together with His6 and either His13 or His14 to form the lower pH Component I of Aβ.
Component II of Aβ is the complex between Cu(II) and His6, His13, and His14, to which an amide O (of Ala2) is also coordinated.
Asp1 does not bind to Cu(II) if three His residues are attached nor to any Cu(I) species to which one or more His residues are bound.
The most stable Cu(I) species is one in which Cu(I) bridges the Nδ of His13 and His14 in a linear fashion.
Cu(I) binds more strongly to Aβ than does Cu(II).
The computed reduction potential that closely matches the experimental value for Cu(II)/Aβ corresponds to reduction of Component II (without Ala2) to the Cu(I) complex after endergonic attachment of His6.
American Psychological Association (APA)
Azimi, Samira& Rauk, Arvi. 2011. On the Involvement of Copper Binding to the N-Terminus of the Amyloid Beta Peptide of Alzheimer's Disease : A Computational Study on Model Systems. International Journal of Alzheimer's Disease،Vol. 2011, no. 2011, pp.1-15.
https://search.emarefa.net/detail/BIM-479846
Modern Language Association (MLA)
Azimi, Samira& Rauk, Arvi. On the Involvement of Copper Binding to the N-Terminus of the Amyloid Beta Peptide of Alzheimer's Disease : A Computational Study on Model Systems. International Journal of Alzheimer's Disease No. 2011 (2011), pp.1-15.
https://search.emarefa.net/detail/BIM-479846
American Medical Association (AMA)
Azimi, Samira& Rauk, Arvi. On the Involvement of Copper Binding to the N-Terminus of the Amyloid Beta Peptide of Alzheimer's Disease : A Computational Study on Model Systems. International Journal of Alzheimer's Disease. 2011. Vol. 2011, no. 2011, pp.1-15.
https://search.emarefa.net/detail/BIM-479846
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-479846