Han Daxiong, Wang Haiyan, Yang Pin
Department of Pharmacy, Medical College of Xiamen University, Xiamen, China.
Biometals. 2008 Apr;21(2):189-96. doi: 10.1007/s10534-007-9107-6. Epub 2007 Jul 13.
Aggregation of the amyloid beta-peptide (Abeta) into insoluble fibrils is a key pathological event in Alzheimer's disease. Cu(II) and Zn(II) ions were reported to be able to induce Abeta aggregation at nearly physiological concentrations in vitro. In this study, the binding modes of Cu(II) and Zn(II) in this process were explored by molecular modeling. In the pre-associated Abeta, Ntau atom of imidazole ring of His14, O atom of carbonyl of main-chain and two O atoms of water occupied the four ligand positions of the complex. While in the aggregated form of Abeta, the His13(N)-Metals-His14(N) bridges were formed through metal cross-linking action. These results would be helpful to put insight on revealing the formation mechanism of pathogenic Abeta aggregates in brain.
淀粉样β肽（Aβ）聚集成不溶性纤维是阿尔茨海默病的关键病理事件。据报道，铜（II）和锌（II）离子在体外接近生理浓度时能够诱导Aβ聚集。在本研究中，通过分子模拟探索了铜（II）和锌（II）在此过程中的结合模式。在预结合的Aβ中，His14咪唑环的Ntau原子、主链羰基的O原子和两个水分子的O原子占据了配合物的四个配体位置。而在Aβ的聚集形式中，通过金属交联作用形成了His13（N）-金属-His14（N）桥。这些结果将有助于深入了解大脑中致病性Aβ聚集体的形成机制。
