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 Aβ16 and Aβ9, and the Aβ16[H6A] and Aβ16[H13A] mutant forms, both in their free amine and N-acetylated forms show that efficient reactivity requires the oxygenation of a CuI-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.

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

Bacchella, Chiara;Dell'Acqua, Simone;Nicolis, Stefania;Monzani, Enrico
;
Casella, Luigi
2021-01-01

Abstract

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 Aβ16 and Aβ9, and the Aβ16[H6A] and Aβ16[H13A] mutant forms, both in their free amine and N-acetylated forms show that efficient reactivity requires the oxygenation of a CuI-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.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11571/1451570
Citazioni
  • ???jsp.display-item.citation.pmc??? 1
  • Scopus 5
  • ???jsp.display-item.citation.isi??? 5
social impact