Department of Chemistry, Missouri University of Science and Technology, Rolla, MO 65409, USA.
J Alzheimers Dis. 2010;20(1):57-66. doi: 10.3233/JAD-2010-1346.
Amyloid-beta (Abeta), the major component of senile plaques in Alzheimer's disease, is known to complex transition metal ions mainly through histidine residues. In this study, using 1H NMR titration experiments, we show that histidine binds strongly to Zn(II), Cu(II), and Fe(III) ions at a biologically relevant pH (pH 7.4), with a stoichiometry of Zn(II): histidine binding of 1:2. The observed deshielding of the chemical shifts and relative line broadening indicate that Fenton-active Cu(II) and Fe(III) bind to histidine relatively more efficiently as compared to Zn(II). Parallel studies showed that glutamic acid and aspartic acid are relatively inefficient in metal ion binding. From these studies, we suggest that Abeta-chelated Zn(II) is readily displaced by Cu(II) and Fe(III) ions and leads to a propagation of oxidative stress.
淀粉样蛋白-β（Abeta）是阿尔茨海默病中老年斑的主要成分，已知其主要通过组氨酸残基与过渡金属离子络合。在这项研究中，我们通过 1H NMR 滴定实验表明，在生物学相关的 pH 值（pH 7.4）下，组氨酸与 Zn(II)、Cu(II)和 Fe(III)离子强烈结合，Zn(II)：组氨酸结合比为 1:2。观察到的化学位移去屏蔽和相对线宽增加表明，与 Zn(II)相比，Fenton 活性的 Cu(II)和 Fe(III)更有效地与组氨酸结合。平行研究表明，谷氨酸和天冬氨酸在金属离子结合方面相对效率较低。根据这些研究，我们认为 Abeta 螯合的 Zn(II)很容易被 Cu(II)和 Fe(III)离子取代，从而导致氧化应激的传播。
