title: Minimal Zn(2+) binding site of amyloid-β.
abstract: Zinc-induced aggregation of amyloid-β peptide (Aβ) is a hallmark molecular feature of Alzheimer's disease. Here we provide direct thermodynamic evidence that elucidates the role of the Aβ 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 Aβ.
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Philipp O
authors.initials: PO
authors.lastname: Tsvetkov
authors.forename: Alexandra A
authors.initials: AA
authors.lastname: Kulikova
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Golovin
authors.forename: Yaroslav V
authors.initials: YV
authors.lastname: Tkachev
authors.forename: Alexander I
authors.initials: AI
authors.lastname: Archakov
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Kozin
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Makarov
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D002151:Calorimetry; D003198:Computer Simulation; D050505:Mutant Proteins / Q000378:metabolism; D011789:Quantum Theory; D013816:Thermodynamics; D015032:Zinc / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D050505:Mutant Proteins; D015032:Zinc