Departamento de Química Orgánica, Universidad de Santiago de Compostela, Santiago de Compostela, Spain.
J Med Chem. 2011 Apr 28;54(8):3081-5. doi: 10.1021/jm101568y. Epub 2011 Mar 31.
β-Secretase is one of the aspartic proteases involved in the formation of amyloid plaques in Alzheimer's disease patients. Our previous results using a combination of surface plasmon resonance experiments with molecular modeling calculations suggested that the Asp dyad in β-secretase bound to hydroxylethylene containing inhibitors adopts a neutral charged state. In this work, we show that the Asp dyad diprotonated state reproduced the binding ranking of a set of these inhibitors better than alternative protonation states.
β-分泌酶是参与阿尔茨海默病患者淀粉样斑块形成的天冬氨酸蛋白酶之一。我们之前的研究结果表明，使用表面等离子体共振实验和分子建模计算相结合的方法，β-分泌酶中与含有羟乙基的抑制剂结合的 Asp 双联体处于中性带电状态。在这项工作中，我们表明，Asp 双联体的二质子化状态比其他质子化状态更好地再现了一组此类抑制剂的结合排序。
