Molecular determinants of allosteric modulation at the M1 muscarinic acetylcholine receptor

Background: BQCA is a selective allosteric modulator of the M1 mAChR. Results: Residues that govern BQCA activity were identified using mutagenesis and molecular modelling. Conclusion: BQCA likely occupies a pocket overlapping prototypical mAChR modulators and gains selectivity through coop- erati...

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Main Authors: Abdul-Ridha, Alaa, López, Laura, Keov, Peter, Thal, David M., Mistry, Shailesh N., Sexton, Patrick M., Lane, J. Robert, Canals, Meritxell, Christopoulos, Arthur
Format: Article
Published: American Society for Biochemistry and Molecular Biology 2014
Online Access:https://eprints.nottingham.ac.uk/30415/
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author Abdul-Ridha, Alaa
López, Laura
Keov, Peter
Thal, David M.
Mistry, Shailesh N.
Sexton, Patrick M.
Lane, J. Robert
Canals, Meritxell
Christopoulos, Arthur
author_facet Abdul-Ridha, Alaa
López, Laura
Keov, Peter
Thal, David M.
Mistry, Shailesh N.
Sexton, Patrick M.
Lane, J. Robert
Canals, Meritxell
Christopoulos, Arthur
author_sort Abdul-Ridha, Alaa
building Nottingham Research Data Repository
collection Online Access
description Background: BQCA is a selective allosteric modulator of the M1 mAChR. Results: Residues that govern BQCA activity were identified using mutagenesis and molecular modelling. Conclusion: BQCA likely occupies a pocket overlapping prototypical mAChR modulators and gains selectivity through coop- erativity with orthosteric ligands. Significance: Understanding the structural basis of BQCA function can provide insight into the design of more tailored allosteric ligands.
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institution University of Nottingham Malaysia Campus
institution_category Local University
last_indexed 2025-11-14T19:08:55Z
publishDate 2014
publisher American Society for Biochemistry and Molecular Biology
recordtype eprints
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spelling nottingham-304152020-05-04T16:41:33Z https://eprints.nottingham.ac.uk/30415/ Molecular determinants of allosteric modulation at the M1 muscarinic acetylcholine receptor Abdul-Ridha, Alaa López, Laura Keov, Peter Thal, David M. Mistry, Shailesh N. Sexton, Patrick M. Lane, J. Robert Canals, Meritxell Christopoulos, Arthur Background: BQCA is a selective allosteric modulator of the M1 mAChR. Results: Residues that govern BQCA activity were identified using mutagenesis and molecular modelling. Conclusion: BQCA likely occupies a pocket overlapping prototypical mAChR modulators and gains selectivity through coop- erativity with orthosteric ligands. Significance: Understanding the structural basis of BQCA function can provide insight into the design of more tailored allosteric ligands. American Society for Biochemistry and Molecular Biology 2014-01-17 Article PeerReviewed Abdul-Ridha, Alaa, López, Laura, Keov, Peter, Thal, David M., Mistry, Shailesh N., Sexton, Patrick M., Lane, J. Robert, Canals, Meritxell and Christopoulos, Arthur (2014) Molecular determinants of allosteric modulation at the M1 muscarinic acetylcholine receptor. Journal of Biological Chemistry, 289 (9). pp. 6067-6079. ISSN 0021-9258 http://www.jbc.org/content/289/9/6067 doi:10.1074/jbc.M113.539080 doi:10.1074/jbc.M113.539080
spellingShingle Abdul-Ridha, Alaa
López, Laura
Keov, Peter
Thal, David M.
Mistry, Shailesh N.
Sexton, Patrick M.
Lane, J. Robert
Canals, Meritxell
Christopoulos, Arthur
Molecular determinants of allosteric modulation at the M1 muscarinic acetylcholine receptor
title Molecular determinants of allosteric modulation at the M1 muscarinic acetylcholine receptor
title_full Molecular determinants of allosteric modulation at the M1 muscarinic acetylcholine receptor
title_fullStr Molecular determinants of allosteric modulation at the M1 muscarinic acetylcholine receptor
title_full_unstemmed Molecular determinants of allosteric modulation at the M1 muscarinic acetylcholine receptor
title_short Molecular determinants of allosteric modulation at the M1 muscarinic acetylcholine receptor
title_sort molecular determinants of allosteric modulation at the m1 muscarinic acetylcholine receptor
url https://eprints.nottingham.ac.uk/30415/
https://eprints.nottingham.ac.uk/30415/
https://eprints.nottingham.ac.uk/30415/