skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Crystallization and preliminary crystallographic studies of the copper-binding domain of the amyloid precursor protein of Alzheimer’s disease

Abstract

The binding of Cu{sup 2+} ions to the copper-binding domain of the amyloid precursor protein of Alzheimer’s disease reduces the production of the amyloid β peptide, which is centrally involved in Alzheimer’s disease. Structural studies of the copper-binding domain will provide a basis for structure-based drug design that might prove useful in treating this devastating disease. Alzheimer’s disease is thought to be triggered by production of the amyloid β (Aβ) peptide through proteolytic cleavage of the amyloid precursor protein (APP). The binding of Cu{sup 2+} to the copper-binding domain (CuBD) of APP reduces the production of Aβ in cell-culture and animal studies. It is expected that structural studies of the CuBD will lead to a better understanding of how copper binding causes Aβ depletion and will define a potential drug target. The crystallization of CuBD in two different forms suitable for structure determination is reported here.

Authors:
 [1]; ;  [2]; ;  [1];  [2];  [2];
  1. Biota Structural Biology Laboratory, St Vincent’s Institute, 9 Princes Street, Fitzroy, Victoria 3065 (Australia)
  2. Department of Pathology, The University of Melbourne, Victoria 3010 (Australia)
Publication Date:
OSTI Identifier:
22356074
Resource Type:
Journal Article
Journal Name:
Acta Crystallographica. Section F
Additional Journal Information:
Journal Volume: 61; Journal Issue: Pt 1; Other Information: PMCID: PMC1952382; PMID: 16508101; PUBLISHER-ID: vr5024; OAI: oai:pubmedcentral.nih.gov:1952382; Copyright (c) International Union of Crystallography 2005; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 1744-3091
Country of Publication:
United Kingdom
Language:
English
Subject:
75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND SUPERFLUIDITY; CLEAVAGE; COPPER; CRYSTALLIZATION; DESIGN; POTENTIALS; PRECURSOR

Citation Formats

Kong, Geoffrey K.-W., Department of Pathology, The University of Melbourne, Victoria 3010, Galatis, Denise, Barnham, Kevin J., The Mental Health Research Institute of Victoria, Parkville, Victoria 3052, Polekhina, Galina, Adams, Julian J., Masters, Colin L., The Mental Health Research Institute of Victoria, Parkville, Victoria 3052, Cappai, Roberto, The Mental Health Research Institute of Victoria, Parkville, Victoria 3052, Centre for Neuroscience, The University of Melbourne, Victoria 3010, Parker, Michael W., and McKinstry, William J., E-mail: wmckinstry@svi.edu.au. Crystallization and preliminary crystallographic studies of the copper-binding domain of the amyloid precursor protein of Alzheimer’s disease. United Kingdom: N. p., 2005. Web. doi:10.1107/S1744309104029744.
Kong, Geoffrey K.-W., Department of Pathology, The University of Melbourne, Victoria 3010, Galatis, Denise, Barnham, Kevin J., The Mental Health Research Institute of Victoria, Parkville, Victoria 3052, Polekhina, Galina, Adams, Julian J., Masters, Colin L., The Mental Health Research Institute of Victoria, Parkville, Victoria 3052, Cappai, Roberto, The Mental Health Research Institute of Victoria, Parkville, Victoria 3052, Centre for Neuroscience, The University of Melbourne, Victoria 3010, Parker, Michael W., & McKinstry, William J., E-mail: wmckinstry@svi.edu.au. Crystallization and preliminary crystallographic studies of the copper-binding domain of the amyloid precursor protein of Alzheimer’s disease. United Kingdom. https://doi.org/10.1107/S1744309104029744
Kong, Geoffrey K.-W., Department of Pathology, The University of Melbourne, Victoria 3010, Galatis, Denise, Barnham, Kevin J., The Mental Health Research Institute of Victoria, Parkville, Victoria 3052, Polekhina, Galina, Adams, Julian J., Masters, Colin L., The Mental Health Research Institute of Victoria, Parkville, Victoria 3052, Cappai, Roberto, The Mental Health Research Institute of Victoria, Parkville, Victoria 3052, Centre for Neuroscience, The University of Melbourne, Victoria 3010, Parker, Michael W., and McKinstry, William J., E-mail: wmckinstry@svi.edu.au. 2005. "Crystallization and preliminary crystallographic studies of the copper-binding domain of the amyloid precursor protein of Alzheimer’s disease". United Kingdom. https://doi.org/10.1107/S1744309104029744.
@article{osti_22356074,
title = {Crystallization and preliminary crystallographic studies of the copper-binding domain of the amyloid precursor protein of Alzheimer’s disease},
author = {Kong, Geoffrey K.-W. and Department of Pathology, The University of Melbourne, Victoria 3010 and Galatis, Denise and Barnham, Kevin J. and The Mental Health Research Institute of Victoria, Parkville, Victoria 3052 and Polekhina, Galina and Adams, Julian J. and Masters, Colin L. and The Mental Health Research Institute of Victoria, Parkville, Victoria 3052 and Cappai, Roberto and The Mental Health Research Institute of Victoria, Parkville, Victoria 3052 and Centre for Neuroscience, The University of Melbourne, Victoria 3010 and Parker, Michael W. and McKinstry, William J., E-mail: wmckinstry@svi.edu.au},
abstractNote = {The binding of Cu{sup 2+} ions to the copper-binding domain of the amyloid precursor protein of Alzheimer’s disease reduces the production of the amyloid β peptide, which is centrally involved in Alzheimer’s disease. Structural studies of the copper-binding domain will provide a basis for structure-based drug design that might prove useful in treating this devastating disease. Alzheimer’s disease is thought to be triggered by production of the amyloid β (Aβ) peptide through proteolytic cleavage of the amyloid precursor protein (APP). The binding of Cu{sup 2+} to the copper-binding domain (CuBD) of APP reduces the production of Aβ in cell-culture and animal studies. It is expected that structural studies of the CuBD will lead to a better understanding of how copper binding causes Aβ depletion and will define a potential drug target. The crystallization of CuBD in two different forms suitable for structure determination is reported here.},
doi = {10.1107/S1744309104029744},
url = {https://www.osti.gov/biblio/22356074}, journal = {Acta Crystallographica. Section F},
issn = {1744-3091},
number = Pt 1,
volume = 61,
place = {United Kingdom},
year = {Sat Jan 01 00:00:00 EST 2005},
month = {Sat Jan 01 00:00:00 EST 2005}
}