Modeling Copper Binding to the Amyloid-beta Peptide at Different pH: Toward a Molecular Mechanism for Cu Reduction (Articolo in rivista)

Type

• Prodotto della ricerca (Classe)
• Articolo in rivista (Classe)

Label

• Modeling Copper Binding to the Amyloid-beta Peptide at Different pH: Toward a Molecular Mechanism for Cu Reduction (Articolo in rivista) (literal)

Anno

• 2012-01-01T00:00:00+01:00 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi

• 10.1021/jp308977s (literal)

Alternative label

• Furlan, S.; Hureau, Christelle; Faller, Peter; La Penna, Giovanni (2012)
  Modeling Copper Binding to the Amyloid-beta Peptide at Different pH: Toward a Molecular Mechanism for Cu Reduction
  in The journal of physical chemistry. B; ACS, American chemical society, Washington, DC (Stati Uniti d'America)
  (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

• Furlan, S.; Hureau, Christelle; Faller, Peter; La Penna, Giovanni (literal)

Pagina inizio

• 11899 (literal)

Pagina fine

• 11910 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#url

• http://dx.doi.org/10.1021/jp308977s (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

• 116 (literal)

Rivista

• ?The ?journal of physical chemistry. B (Rivista)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#pagineTotali

• 12 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo

• 39 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

• LCC - Laboratory of coordination chemistry, CNRS - National Center for Scientific Research, 205 route de Narbonne, F-31077 Toulouse, France ICCOM - Institute for chemistry of organo-metallic compounds, CNR - National Research Council of Italy, via Madonna del Piano 10, I-50019 Sesto Fiorentino, Firenze, Italy (literal)

Titolo

• Modeling Copper Binding to the Amyloid-beta Peptide at Different pH: Toward a Molecular Mechanism for Cu Reduction (literal)

Abstract

• Oxidative stress, including the production of reactive oxygen species (ROS), has been reported to be a key event in the etiology of Alzheimer's disease (AD). Cu has been found in high concentrations in amyloid plaques, a hallmark of AD, where it is bound to the main constituent amyloid-? (A?) peptide. Whereas it has been proposed that Cu-A? complexes catalyze the production of ROS via redox-cycling between the Cu(I) and Cu(II) state, the redox chemistry of Cu-A? and the precise mechanism of redox reactions are still unclear. Because experiments indicate different coordination environments for Cu(II) and Cu(I), it is expected that the electron is not transferred between Cu-A? and reactants in a straightforward manner but involves structural rearrangement. In this work the structures indicated by experimental data are modeled at the level of modern densityfunctional theory approximations. Possible pathways for Cu(II) reduction in different coordination sites are investigated by means of first-principles molecular dynamics simulations in the water solvent and at room temperature. The models of the ligand reorganization around Cu allow the proposal of a preferential mechanism for Cu-A? complex reduction at physiological pH. Models reveal that for efficient reduction the deprotonated amide N in the Ala 2-Glu 3 peptide bond has to be protonated and that interactions in the second coordination sphere make important contributions to the reductive pathway, in particular the interaction between COO- and NH2 groups of Asp 1. The proposed mechanism is an important step forward to a clear understanding of the redox chemistry of Cu-A?, a difficult task for spectroscopic approaches as the Cu-peptide interactions are weak and dynamical in nature. (literal)

Editore

• ACS, American chemical society (Editore)

Prodotto di

• Istituto di chimica dei composti organo metallici (ICCOM) (Istituto)
• Catalisi ed elettrocatalisi per la produzione sostenibile di energia e la trasformazione di risorse rinnovabili (PM.P03.001.001) (Modulo)

Autore CNR

• GIOVANNI LA PENNA (Unità di personale interno)

Insieme di parole chiave

• Keywords of "Modeling Copper Binding to the Amyloid-beta Peptide at Different pH: Toward a Molecular Mechanism for Cu Reduction" (Insieme di parole chiave)

Incoming links:

Prodotto

• Istituto di chimica dei composti organo metallici (ICCOM) (Istituto)
• Catalisi ed elettrocatalisi per la produzione sostenibile di energia e la trasformazione di risorse rinnovabili (PM.P03.001.001) (Modulo)

Autore CNR di

• GIOVANNI LA PENNA (Unità di personale interno)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#rivistaDi

• ?The ?journal of physical chemistry. B (Rivista)

Editore di

• ACS, American chemical society (Editore)

Insieme di parole chiave di

• Keywords of "Modeling Copper Binding to the Amyloid-beta Peptide at Different pH: Toward a Molecular Mechanism for Cu Reduction" (Insieme di parole chiave)