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Alanine-2 carbonyl is an oxygen ligand in Cu2+ coordination of Alzheimer's disease amyloid-beta peptide--relevance to N-terminally truncated forms.
J Am Chem Soc. 2009 Jul 01; 131(25):8760-1.JA

Abstract

Copper interactions with the beta-amyloid peptide (Abeta) are believed to play a role in Alzheimer's disease (AD), in particular due to production of reactive oxygen species and Cu(2+)-mediated oligomerization. To understand the role that copper might play in these processes, a detailed knowledge of the fundamental Cu(2+)/Abeta interactions is essential. To date, the identity of the oxygen ligand(s) involved in Cu(2+) coordination by Abeta has remained unclear. Here, we have used site-specific (13)C and (15)N 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 Cu(2+) coordination modes of Abeta. Polarization of the carbonyl moiety by Cu(2+) could promote amide hydrolysis and cleavage of the peptide bond between Ala2 and Glu3, providing a chemical mechanism for the generation of truncated Abeta 3-40/42 species found in AD plaques.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Drew SC
Department of Pathology and Neuroproteomics Platform, National Neuroscience Facility, The Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria 3010, Australia. sdrew@unimelb.edu.au
Masters CL
No affiliation info available
Barnham KJ
No affiliation info available

MeSH

AlanineAlzheimer DiseaseAmyloid beta-PeptidesCopperHumansHydrogen-Ion ConcentrationLigandsMolecular StructureOxygen

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19496610

Citation

Drew, Simon C., et al. "Alanine-2 Carbonyl Is an Oxygen Ligand in Cu2+ Coordination of Alzheimer's Disease Amyloid-beta Peptide--relevance to N-terminally Truncated Forms." Journal of the American Chemical Society, vol. 131, no. 25, 2009, pp. 8760-1.
Drew SC, Masters CL, Barnham KJ. Alanine-2 carbonyl is an oxygen ligand in Cu2+ coordination of Alzheimer's disease amyloid-beta peptide--relevance to N-terminally truncated forms. J Am Chem Soc. 2009;131(25):8760-1.
Drew, S. C., Masters, C. L., & Barnham, K. J. (2009). Alanine-2 carbonyl is an oxygen ligand in Cu2+ coordination of Alzheimer's disease amyloid-beta peptide--relevance to N-terminally truncated forms. Journal of the American Chemical Society, 131(25), 8760-1. https://doi.org/10.1021/ja903669a
Drew SC, Masters CL, Barnham KJ. Alanine-2 Carbonyl Is an Oxygen Ligand in Cu2+ Coordination of Alzheimer's Disease Amyloid-beta Peptide--relevance to N-terminally Truncated Forms. J Am Chem Soc. 2009 Jul 1;131(25):8760-1. PubMed PMID: 19496610.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Alanine-2 carbonyl is an oxygen ligand in Cu2+ coordination of Alzheimer's disease amyloid-beta peptide--relevance to N-terminally truncated forms. AU - Drew,Simon C, AU - Masters,Colin L, AU - Barnham,Kevin J, PY - 2009/6/6/entrez PY - 2009/6/6/pubmed PY - 2009/9/16/medline SP - 8760 EP - 1 JF - Journal of the American Chemical Society JO - J Am Chem Soc VL - 131 IS - 25 N2 - Copper interactions with the beta-amyloid peptide (Abeta) are believed to play a role in Alzheimer's disease (AD), in particular due to production of reactive oxygen species and Cu(2+)-mediated oligomerization. To understand the role that copper might play in these processes, a detailed knowledge of the fundamental Cu(2+)/Abeta interactions is essential. To date, the identity of the oxygen ligand(s) involved in Cu(2+) coordination by Abeta has remained unclear. Here, we have used site-specific (13)C and (15)N 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 Cu(2+) coordination modes of Abeta. Polarization of the carbonyl moiety by Cu(2+) could promote amide hydrolysis and cleavage of the peptide bond between Ala2 and Glu3, providing a chemical mechanism for the generation of truncated Abeta 3-40/42 species found in AD plaques. SN - 1520-5126 UR - https://www.unboundmedicine.com/medline/citation/19496610/Alanine_2_carbonyl_is_an_oxygen_ligand_in_Cu2+_coordination_of_Alzheimer's_disease_amyloid_beta_peptide__relevance_to_N_terminally_truncated_forms_ L2 - https://doi.org/10.1021/ja903669a DB - PRIME DP - Unbound Medicine ER -