How To Figure Out Binding From K App

Identification of a novel high affinity copper binding site in the APP(145–155) fragment of amyloid precursor protein

Author affiliations

* Corresponding authors

^a Department of Chemistry and the NMR Center, University of Siena, via Moro, 53100 Siena, Italy
E-mail: valensin@unisi.it

^b Faculty of Chemistry, University of Wroclaw, F. Joliot-Curie 14, 50-383 Wroclaw, Poland
E-mail: henrykoz@wchuwr.chem.uni.wroc.pl

^c Faculty of Chemistry, University of Gdansk, 80-952 Gdansk, Poland

Abstract

The copper(II) binding features of the APP(145–155) and APP(145–157) fragments of the amyloid precursor protein, Ac-Glu-Thr-His-Leu-His-Trp-His-Thr-Val-Ala-Lys-NH ₂ and Ac-Glu-Thr-His-Leu-His-Trp-His-Thr-Val-Ala-Lys-Glu-Thr-NH ₂ were studied by NMR spectroscopy and NMR findings were supported by UV-vis, CD and EPR spectra. Potentiometric measurements were performed only for the more soluble Ac-Glu-Thr-His-Leu-His-Trp-His-Thr-Val-Ala-Lys-Glu-Thr-NH ₂ peptide fragment. The following was shown: (i) the imidazole rings of all the three His residues are involved in metal coordination; (ii) metal binding induces ionisation of Leu-148 and His-149 amide nitrogens that complete the donor set to copper(II) in the species dominant at neutral pH; (iii) the unusual coordination scheme of the His-Xxx-His-Xxx-His consensus sequence justifies the high specificity for Cu(II) when compared to SOD-like or albumin-like peptides or even in amyloid Aβ fragments. The present findings may represent the key for interpreting the observed requirement of His residues conservation for the redox cycling between Cu(II) and Cu(I) by soluble APP.

Graphical abstract: Identification of a novel high affinity copper binding site in the APP(145–155) fragment of amyloid precursor protein

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Article information

DOI: https://doi.org/10.1039/B312411H
Article type: Paper
Submitted: 06 Oct 2003
Accepted: 03 Nov 2003
First published: 18 Nov 2003

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Dalton Trans. , 2004, 16-22

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Identification of a novel high affinity copper binding site in the APP(145–155) fragment of amyloid precursor protein

D. Valensin, F. M. Mancini, M. Łuczkowski, A. Janicka, K. Wiśniewska, E. Gaggelli, G. Valensin, L. Łankiewicz and H. Kozlowski, Dalton Trans., 2004, 16 DOI: 10.1039/B312411H

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