title: Importance of dynamical processes in the coordination chemistry and redox conversion of copper amyloid-beta complexes.
abstract: Interaction of Cu ions with the amyloid-beta (Abeta) peptide is linked to the development of Alzheimer's disease; hence, determining the coordination of Cu(I) and Cu(II) ions to Abeta and the pathway of the Cu(I)(Abeta)/Cu(II)(Abeta) redox conversion is of great interest. In the present report, we use the room temperature X-ray absorption near edge structure to show that the binding sites of the Cu(I) and Cu(II) complexes are similar to those previously determined from frozen-solution studies. More precisely, the Cu(I) is coordinated by the imidazole groups of two histidine residues in a linear fashion. However, an NMR study unravels the involvement of all three histidine residues in the Cu(I) binding due to dynamical exchange between several set of ligands. The presence of an equilibrium is also responsible for the complex redox process observed by cyclic voltammetry and evidenced by a concentration-dependent electrochemical response.
authors.affiliation: CNRS, LCC (Laboratoire de Chimie de Coordination), 205, route de Narbonne, 31077 Toulouse, France. hureau@lcc-toulouse.fr
authors.forename: Christelle
authors.initials: C
authors.lastname: Hureau
authors.forename: Véronique
authors.initials: V
authors.lastname: Balland
authors.forename: Yannick
authors.initials: Y
authors.lastname: Coppel
authors.forename: Pier Lorenzo
authors.initials: PL
authors.lastname: Solari
authors.forename: Emiliano
authors.initials: E
authors.lastname: Fonda
authors.forename: Peter
authors.initials: P
authors.lastname: Faller
mesh_terms: D000544:Alzheimer Disease / Q000517:prevention & control; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D002614:Chelating Agents / Q000378:metabolism*; D003300:Copper / Q000737:chemistry / Q000378:metabolism*; D055664:Electrochemical Techniques; D006639:Histidine / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D019906:Nuclear Magnetic Resonance, Biomolecular; D009942:Organometallic Compounds; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D044367:Phase Transition; D013054:Spectrophotometry, Atomic
chemical_list: D016229:Amyloid beta-Peptides; D002614:Chelating Agents; D009942:Organometallic Compounds; D010446:Peptide Fragments; D006639:Histidine; D003300:Copper