Alanine-2 Carbonyl is an Oxygen Ligand in Cu2+ Coordination of Alzheimer’s Disease Amyloid-β Peptide − Relevance to N-Terminally Truncated Forms
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- 作者：Simon C. Drew ; Colin L. Masters ; Kevin J. Barnham
- 刊名：Journal of the American Chemical Society
- 出版年：2009
- 出版时间：July 1, 2009
- 年：2009
- 卷：131
- 期：25
- 页码：8760-8761
- 全文大小：166K
- 年卷期：v.131,no.25(July 1, 2009)
- ISSN：1520-5126
文摘
Copper interactions with the β-amyloid peptide (Aβ) are believed to play a role in Alzheimer’s disease (AD), in particular due to production of reactive oxygen species and Cu2+-mediated oligomerization. To understand the role that copper might play in these processes, a detailed knowledge of the fundamental Cu2+/Aβ interactions is essential. To date, the identity of the oxygen ligand(s) involved in Cu2+ coordination by Aβ has remained unclear. Here, we have used site-specific 13C and 15N labeling in conjunction with hyperfine sublevel correlation (HYSCORE) spectroscopy to unambiguously identify the carbonyl of Alanine-2 as an oxygen ligand in one of the pH-dependent Cu2+ coordination modes of Aβ. Polarization of the carbonyl moiety by Cu2+ could promote amide hydrolysis and cleavage of the peptide bond between Ala2 and Glu3, providing a chemical mechanism for the generation of truncated Aβ 3−40/42 species found in AD plaques.