Molecular modeling of the inhibitory mechanism of copper(II) on aggregation of amyloid β-peptide

被引：0
作者：
Yong Jiao
Daxiong Han
Pin Yang
机构：
[1] Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education,Institute of Molecular Science
[2] Shanxi University,undefined
来源：
Science in China Series B: Chemistry | 2005年 / 48卷
关键词：
copper(II); amyloid β-peptide; inhibitory mechanism; Alzheimer’s disease; molecular modeling;
D O I：
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学科分类号：
摘要：
Aggregation of amyloid β-peptide (Aβ) into insoluble fibrils is a key pathological event in Alzheimer’s disease (AD). Under certain conditions, Cu(II) exhibits strong inhibitory effect on the Zn(II)-induced aggregation, which occurs significantly even at nearly physiological concentrations of zinc ion in vitro. Cu(II) is considered as a potential factor in the normal brain preventing Aβ from aggregating. The possible mechanism of the inhibitory effect of Cu(II) is investigated for the first time by molecular modeling method. In the mono-ring mode, the Y10 residue promotes typical quasi-helix conformations of Aβ. Specially, [Cu-H13(NTT)-Y10(OH)] complex forms a local 3.010 helix conformation. In the multi-ring mode, the side chains of Q15 and E11 residues collaborate harmoniously with other chelating ligands producing markedly low energies and quasi-helix conformations. [Cu-3N-Q15(O)-E11(O1)] and [Cu-H13(NTT)-Y10(OH)] complex with quasi-helix conformations may prefer soluble forms in solution. In addition, hydrogen-bond interactions may be the main driving force for Aβ aggregation. All the results will provide helpful clues for an improved understanding of the role of Cu(II) in the pathogenesis of AD and contribute to the development of an “anti-amyloid” therapeutic strategy.
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页码：580 / 590
页数：10
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