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Characterization of the Zn II Binding to the Peptide Amyloid‐β 1–16 linked to Alzheimer's Disease
Author(s) -
Mekmouche Yasmina,
Coppel Yannick,
Hochgräfe Katja,
Guilloreau Luc,
Talmard Christine,
Mazarguil Honoré,
Faller Peter
Publication year - 2005
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200500057
Subject(s) - chemistry , circular dichroism , peptide , random coil , zinc , ligand (biochemistry) , crystallography , dissociation constant , histidine , nuclear magnetic resonance spectroscopy , tyrosine , metal ions in aqueous solution , metal , stereochemistry , amino acid , biochemistry , receptor , organic chemistry
Aggregation of the human peptide amyloid‐β (Aβ) is a key event in Alzheimer's disease (AD). Zinc ions play an important role in AD and in Aβ aggregation. In vitro, Zn II binds to Aβ and accelerates its aggregation. In this work we have investigated Zn II binding to the synthetic peptide Aβ 1–16 , which contains the metal‐binding domain of Aβ. Cd II was used to probe the Zn II site. Aβ 1–16 bound one equivalent of Zn II with an apparent dissociation constant ( K d ) of 10 −4 M . This K d value is in the same range as the Zn concentration needed to precipitate Aβ. Circular dichroism and NMR indicated predominantly random‐coil secondary structures of apo‐Aβ 1–16 , Zn II –A β 1–16 and Cd II –A β 1–16 , which were all highly dynamic and flexible. The three histidines at positions 6, 13 and 14 were suggested to be ligands to Zn II and Cd II . Evidence that the aspartate at position 1 served as a fourth ligand to Zn II and Cd II was found at pH 8.7. 111 Cd II NMR showed a resonance at 84 ppm, in line with a mixed oxygen‐/nitrogen‐ligand environment. The tyrosine at position 10 could be excluded as a ligand.