Minimal Zn(2+) binding site of amyloid-?.

ABSTRACT: Zinc-induced aggregation of amyloid-? peptide (A?) is a hallmark molecular feature of Alzheimer's disease. Here we provide direct thermodynamic evidence that elucidates the role of the A? 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?.

SUBMITTER: Tsvetkov PO 

PROVIDER: S-EPMC2980701 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature