Structural characterization of Cu2+, Ni2+ and Zn2+ binding sites of model peptides associated with neurodegenerative diseases

Cross‐Talk Between the Octarepeat Domain and the Fifth Binding Site of Prion Protein Driven by the Interaction of Copper(II) with the N‐terminus

“…[67,78,[105][106][107] . At pH 7.4 three metal-coordination modes have been found so far within the tetraoctarepeat domain: [81] Two copper(II) binding sites, centred around His96 and His111, have also been found for the amyloidogenic PrP region, [67,69,78] with His111 having a higher affinity for copper(II).…”

“…[67,78,[105][106][107] . At pH 7.4 three metal-coordination modes have been found so far within the tetraoctarepeat domain: [81] Two copper(II) binding sites, centred around His96 and His111, have also been found for the amyloidogenic PrP region, [67,69,78] with His111 having a higher affinity for copper(II). [72,73,75,90,91,108] (N im ,N À ,N À ) is the main metal-binding mode experienced by Cu 2+ , although there is no general agreement on the contribution of additional donor atoms.…”

“…[44,[67][68][69] There is a general consensus that PrP can bind at least six copper(II) ions: [70][71][72][73][74][75][76] four copper-binding sites are present in the octarepeat region (residues 60-91), which is composed, in the human sequence, of four identical PHGGGWGQ units, with the histidine of each repeat being the primary copper(II) anchoring site. [77][78][79][80][81][82][83][84][85][86][87] Moreover, the hPrP91-127 region, which is next to the repeat domain, provides two further copper(II) binding sites, each associated with a histidine residue, His96 and His111, respectively. [67,70,72,73,75,76,[88][89][90][91][92][93][94][95][96] Although there is no general consensus, most of the results obtained so far indicate His111 as the preferential, if not exclusive, copper(II) binding site.…”

NMR metabolomic investigation of astrocytes interacted with Aβ42 or its complexes with either copper(II) or zinc(II)

“…A huge number of investigations have delineated the metal coordination spheres for monomeric form of Aβ (see for examples Refs. [71,72]). On the contrary very little is known about metal binding structure in Aβ aggregates and the exact metal binding sites of Aβ fibrils are still controversial [73].…”

Especiação de cobre e zinco em urina: importância dos metais em doenças neurodegenerativas

“…Apesar de ainda não serem conhecidos todos os processos bioquímicos e/ou fisiológicos que conduzem ao desenvolvimento destas desordens, sabe-se hoje que as principais doenças neurodegenerativas, tais como a doença de Alzheimer e a doença de Parkinson, apresentam algumas semelhanças, especialmente no que respeita à deposição intra ou extracelular de emaranhados proteicos. 1 A doença de Alzheimer é uma doença progressiva e irreversível, que começa por atingir a memória e com a evolução acaba por afetar outras funções mentais. Um doente de Alzheimer, após diagnosticada a doença, resiste em média 8 anos.…”