Journal article

Copper-dependent inhibition of cytochrome c oxidase by A beta(1-42) requires reduced methionine at residue 35 of the A beta peptide

Peter J Crouch, Kevin J Barnham, James A Duce, Rachel E Blake, Colin L Masters, Ian A Trounce



By altering key amino acid residues of the Alzheimer's disease-associated amyloid-beta peptide, we investigated the mechanism through which amyloid-beta inhibits cytochrome c oxidase (EC Native amyloid-beta inhibited cytochrome oxidase by up to 65%, and the level of inhibition was determined by the period of amyloid-beta ageing before the cytochrome oxidase assay. Substituting tyrosine-10 with alanine did not affect maximal enzyme inhibition, but the altered peptide required a longer period of ageing. By contrast, oxidizing the sulfur of methionine-35 to a sulfoxide, or substituting methionine-35 with valine, completely abrogated the peptide's inhibitory potential towards cytochrom..

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