Zinc-induced aggregation of amyloid-β peptide (Aβ) is a hallmark molecular feature of Alzheimer's disease. The team headed by Philippe Tsvetkov provided direct thermodynamic evidence that elucidates the role of the Aβ region 6–14 as the minimal Zn2+ binding site wherein the ion is coordinated by His6, Glu11, His13, and His14. 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 Zn2+-induced aggregation of Aβ.
Alzheimer's disease, a fatal neurodegenerative disorder of the elderly, is characterized by extracellular depositions of amyloid-β peptide (Aβ) saturated with metal ions. It is believed that Zn2+ ions play a key role in pathological aggregation of Aβ and therefore affect the pathogenesis of Alzheimer's disease. The insights into molecular mechanism of Zinc-induced aggregation allow to consider Aβ(11–14) tetrapeptide as a primary Zn2+-recognition site of Aβ and an important drug target candidate to prevent Zn2+-induced aggregation of Aβ.
Minimal Zn2+ Binding Site of Amyloid-β
Philipp O. Tsvetkov, Alexandra A. Kulikova, Andrey V. Golovin, Yaroslav V. Tkachev, Alexander I. Archakov, Sergey A. Kozin, and Alexander A. Makarov
Biophysical Journal, Volume 99, Issue 10, L84-L86, 17 November 2010