Local atomic and electronic structure of Cu (I,II) binding site in amyloid beta peptide: theoretical HERFD XANES study

Copper is an essential trace element. Being a part of many enzymes and proteins, it is involved in their life cycle [1]. However, copper can be toxic if its homeostasis is not controlled. Some known pathologies associated with... [ view full abstract ]

Copper is an essential trace element. Being a part of many enzymes and proteins, it is involved in their life cycle [1]. However, copper can be toxic if its homeostasis is not controlled. Some known pathologies associated with the abnormal copper homeostasis are Wilson and Menkes diseases and neurodegenerative disorders such as Alzheimer's or Prion diseases [2]. Currently, Alzheimer's disease is considered one of the most common progressive neurodegenerative disorders. It is known that Alzheimer’s disease brain is characterized by elevated levels of oxidative stress and high levels of redox active transition metals such as Cu and Fe [3].

Atomic structure of copper (I,II) binding site in Aβ peptide was studied by means of combination techniques of quantum chemical calculations and advanced theoretical XANES analysis. Theoretical models of copper Cu (I, II) binding site in Aβ peptide were calculated in ADF (Amsterdam Density Functional) package [4]. The calculation of theoretical X-ray absorption spectra was carried out in an accelerated version FDMNES code [5]. Acceleration software for FDMNES code was developed in International Research Center "Smart materials".

In addition, for obtained models high energy resolution fluorescence detected X-ray absorption near edge structure (HERFD XANES) spectra calculations was carried out. Information obtained from HERFD XANES spectra gives more detailed information on local atomic and electronic structure of protein samples compared traditional XANES spectra.

The main structural parameters such as interatomic distances and bond angles for both copper (I, II) binding site configurations of amyloid beta were obtained.

This study was supported by the Russian Foundation for Basic Research, project № 16-32-00568.

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