Molecular determinants of allosteric modulation at the M1 muscarinic acetylcholine receptor

Article, Other literature type English OPEN
Abdul-Ridha, Alaa ; López, Laura ; Keov, Peter ; Thal, David M. ; Mistry, Shailesh N. ; Sexton, Patrick M. ; Lane, J. Robert ; Canals, Meritxell ; Christopoulos, Arthur (2014)
  • Publisher: American Society for Biochemistry and Molecular Biology
  • Related identifiers: doi: 10.1074/jbc.M113.539080
  • Subject: Signal Transduction

Background: BQCA is a selective allosteric modulator of the M1 mAChR.\ud Results: Residues that govern BQCA activity were identified using mutagenesis and molecular modelling.\ud Conclusion: BQCA likely occupies a pocket overlapping prototypical mAChR modulators and gains selectivity through coop- erativity with orthosteric ligands.\ud Significance: Understanding the structural basis of BQCA function can provide insight into the design of more tailored allosteric ligands.