NMR Studies of Zinc, Copper, and Iron Binding to Histidine, the Principal Metal Ion Complexing Site of Amyloid-ß Peptide

Abstract

Amyloid-ß (Aß), the major component of senile plaques in Alzheimer's disease, is known to complex transition metal ions mainly through histidine residues. In this study, using 1H NMR titration experiments, we show that histidine binds strongly to Zn(II), Cu(II), and Fe(III) ions at a biologically relevant pH (pH 7.4), with a stoichiometry of Zn(II): histidine binding of 1:2. The observed deshielding of the chemical shifts and relative line broadening indicate that Fenton-active Cu(II) and Fe(III) bind to histidine relatively more efficiently as compared to Zn(II). Parallel studies showed that glutamic acid and aspartic acid are relatively inefficient in metal ion binding. From these studies, we suggest that Aß-chelated Zn(II) is readily displaced by Cu(II) and Fe(III) ions and leads to a propagation of oxidative stress.

Department(s)

Chemistry

Keywords and Phrases

Alzheimer's disease; amyloid-ß peptide; aspartic acid; Fenton reaction; glutamic acid; histidine; metal ion chelation; NMR titrations; oxidative stress; tyrosine

International Standard Serial Number (ISSN)

1387-2877

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2010 IOS Press, All rights reserved.

Publication Date

01 Nov 2010

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