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Issue 30, 2009
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Modeling of the Zn2+ binding in the 1–16 region of the amyloid β peptide involved in Alzheimer’s disease

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Abstract

Zinc ions are found at mM concentration in amyloid plaques of Alzheimer’s disease and the role of zinc in protein oligomerization is the object of intense investigations. As an in vitro model for studying interactions between Zn2+ and the Aβ peptide, that is the main component of plaques, the N- and C-termini protected Aβ(1–16) fragment has been chosen because reliable spectroscopic studies in water solution are possible due to the low propensity for oligomerization at pH ∼ 6.5, and because all the Zn binding sites of Aβ have been identified in the 1–16 region. In this work we present the results of first principle simulations of several initial models of Zn-Aβ(1–16) complexes. The NMR results about the same system, where His 6, 13, 14 and Glu 11 side-chains coordinate the Zn ion, are strongly supported by these models. Coordination of Asp 1 to Zn drives the complex towards the expulsion of one of initially bonded His side-chains. Coordination of Tyr 10 to Zn is possible only when Tyr 10 is deprotonated. The interplay between physico-chemical properties of the Aβ ligand and the Zn coordination is discussed.

Graphical abstract: Modeling of the Zn2+ binding in the 1–16 region of the amyloid β peptide involved in Alzheimer’s disease

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Publication details

The article was received on 18 Dec 2008, accepted on 24 Apr 2009 and first published on 27 May 2009


Article type: Paper
DOI: 10.1039/B822771C
Citation: Phys. Chem. Chem. Phys., 2009,11, 6468-6481
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    Modeling of the Zn2+ binding in the 1–16 region of the amyloid β peptide involved in Alzheimer’s disease

    S. Furlan and G. La Penna, Phys. Chem. Chem. Phys., 2009, 11, 6468
    DOI: 10.1039/B822771C

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