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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

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...

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Autores principales: Azimi, Samira, Rauk, Arvi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE-Hindawi Access to Research 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3235578/
https://www.ncbi.nlm.nih.gov/pubmed/22191059
http://dx.doi.org/10.4061/2011/539762
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author Azimi, Samira
Rauk, Arvi
author_facet Azimi, Samira
Rauk, Arvi
author_sort Azimi, Samira
collection PubMed
description 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 N(δ) 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.
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spelling pubmed-32355782011-12-21 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 Azimi, Samira Rauk, Arvi Int J Alzheimers Dis Research Article 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 N(δ) 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. SAGE-Hindawi Access to Research 2011 2011-12-01 /pmc/articles/PMC3235578/ /pubmed/22191059 http://dx.doi.org/10.4061/2011/539762 Text en Copyright © 2011 S. Azimi and A. Rauk. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3235578/
https://www.ncbi.nlm.nih.gov/pubmed/22191059
http://dx.doi.org/10.4061/2011/539762
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