Minimal Zn 2+ Binding Site of Amyloid- β

Abstract

Zinc-induced aggregation of amyloid- β peptide (A β) is a hallmark molecular feature of Alzheimer's disease. Here we provide direct thermodynamic evidence that elucidates the role of the A β region 6–14 as the minimal Zn 2+ binding site wherein the ion is coordinated by His 6, Glu 11, His 13, and His 14. With the help of isothermal titration calorimetry and quantum mechanics/molecular mechanics simulations, the region 11–14 was determined as the primary zinc recognition site and considered an important drug-target candidate to prevent Zn 2+-induced aggregation of A β.