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

摘要: The copper(II) binding features of the APP(145-155) and APP(145-157) fragments amyloid precursor protein, Ac-Glu-Thr-His-Leu-His-Trp-His-Thr-Val-Ala-Lys-NH2 Ac-Glu-Thr-His-Leu-His-Trp-His-Thr-Val-Ala-Lys-Glu-Thr-NH2 were studied by NMR spectroscopy findings supported UV-vis, CD EPR spectra. Potentiometric measurements performed only for more soluble peptide fragment. following was shown: (i) imidazole rings all three His residues are involved in metal coordination; (ii) induces ionisation Leu-148 His-149 amide nitrogens that complete donor set to species dominant at neutral pH; (iii) unusual coordination scheme His-Xxx-His-Xxx-His consensus sequence justifies high specificity Cu(II) when compared SOD-like or albumin-like peptides even Abeta fragments. present may represent key interpreting observed requirement conservation redox cycling between Cu(I) APP.