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A Cu-bis(imidazole) Substrate Intermediate Is the Catalytically Competent Center for Catechol Oxidase Activity of Copper Amyloid-β

[Image: see text] Interaction of copper ions with Aβ peptides alters the redox activity of the metal ion and can be associated with neurodegeneration. Many studies deal with the characterization of the copper binding mode responsible for the reactivity. Oxidation experiments of dopamine and related...

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Detalles Bibliográficos
Autores principales: Bacchella, Chiara, Dell’Acqua, Simone, Nicolis, Stefania, Monzani, Enrico, Casella, Luigi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2021
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023651/
https://www.ncbi.nlm.nih.gov/pubmed/33405903
http://dx.doi.org/10.1021/acs.inorgchem.0c02243
Descripción
Sumario:[Image: see text] Interaction of copper ions with Aβ peptides alters the redox activity of the metal ion and can be associated with neurodegeneration. Many studies deal with the characterization of the copper binding mode responsible for the reactivity. Oxidation experiments of dopamine and related catechols by copper(II) complexes with the N-terminal amyloid-β peptides Aβ(16) and Aβ(9), and the Aβ(16)[H6A] and Aβ(16)[H13A] mutant forms, both in their free amine and N-acetylated forms show that efficient reactivity requires the oxygenation of a Cu(I)-bis(imidazole) complex with a bound substrate. Therefore, the active intermediate for catechol oxidation differs from the proposed “in-between state” for the catalytic oxidation of ascorbate. During the catechol oxidation process, hydrogen peroxide and superoxide anion are formed but give only a minor contribution to the reaction.