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Chem Res Toxicol. 2004 Mar;17(3):325-9.

Mutation of the Phe20 residue in Alzheimer's amyloid beta-peptide might decrease its toxicity due to disruption of the Met35-cupric site electron transfer pathway.

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  • 1Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw, Poland. pogo@orange.ichtj.waw.pl

Abstract

It has been proposed that the Met residue in the C-terminal domain of the Alzheimer's disease beta-amyloid peptide (betaA) serves as a source of electrons for the Cu(II)-catalyzed reduction of molecular oxygen to hydrogen peroxide. Mechanistically, this process would require the long distance electron transfer from the thioether sulfur to the peptide-bound copper. Therefore, the electron transfer pathways between the Met35 sulfur atom and the cupric site in the N terminus of betaA congeners have been analyzed applying semiclassical models of long distance electron transfer. Simulations performed for several betaA conformers collected along the 6 ns Langevin Dynamics trajectories suggest that the presence of the Phe20 residue in the peptide is required for feasibility of the electron transfer. Thus, I would like to propose the mutation Phe20Ala in betaA as a potential way to reduce its neurotoxicity.

PMID:
15025502
[PubMed - indexed for MEDLINE]
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