Wydział Chemii

Marek Łuczkowski

K. Wiśniewska

L. Łankiewicz

Henryk Kozłowski

2002

Journal of the Chemical Society, Dalton Transactions

2266-2268

10.1039/B203284H

Naukowa

Angielski

Artykuł

The βA4 amyloid precursor protein fragment situated in the cysteine-rich region is a very effective binding site for Cu²⁺ ions due to the presence of three His residues in the His–Xaa–His–Yaa–His sequence.The βA4 amyloid precursor protein (APP), a multifunctional glycoprotein, is a source of the characteristic βA4 amyloid deposits found in Alzheimer's disease.¹ APP is known to bind to Zn²⁺ ions, which may modulate its interactions with heparin.² Studies by Multhaup et al.^3–6 have shown that the βA4 amyloid precursor protein binds very effectively to Cu²⁺ ions and then reduces them to Cu⁺, producing hydrogen peroxide. The copper-binding also results in a site-specific fragmentation of APP, which could be an important process during Alzheimer pathology.⁵ The main cause of the specific Cu²⁺ ion binding seems to be the presence of His residues in the cysteine-rich region of APP, while redox reactions are induced by two cysteine residues at positions 144 and 158.^5,6 The –His–Xaa–His– sequence, present in the SOD1 copper-binding centre for example, could be a major factor for metal ion binding by APP.³ In this work we have tested the specificity of a three His residue site, –His–Leu–His–Trp–His–, which is present in a cysteine-rich region of APP, using potentiometric and spectroscopic techniques (absorption, EPR and CD spectra). To model the protein binding site we have used a pentapeptide fragment protected at the N- and C-termin.

https://doi.org/10.1039/B203284H

https://www.rsc.org/