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- Title
The Aminotriazole Antagonist Cmpd‐1 Stabilises a Distinct Inactive State of the Adenosine 2A Receptor.
- Authors
Landin, Erik J. B.; Lovera, Silvia; de Fabritiis, Gianni; Kelm, Sebastian; Mercier, Joël; McMillan, David; Sessions, Richard B.; Taylor, Richard J.; Sands, Zara A.; Joedicke, Lisa; Crump, Matthew P.
- Abstract
The widely expressed G‐protein coupled receptors (GPCRs) are versatile signal transducer proteins that are attractive drug targets but structurally challenging to study. GPCRs undergo a number of conformational rearrangements when transitioning from the inactive to the active state but have so far been believed to adopt a fairly conserved inactive conformation. Using 19F NMR spectroscopy and advanced molecular dynamics simulations we describe a novel inactive state of the adenosine 2A receptor which is stabilised by the aminotriazole antagonist Cmpd‐1. We demonstrate that the ligand stabilises a unique conformation of helix V and present data on the putative binding mode of the compound involving contacts to the transmembrane bundle as well as the extracellular loop 2.
- Subjects
MOLECULAR spectroscopy; G protein coupled receptors; ADENOSINES; MOLECULAR dynamics; NUCLEAR magnetic resonance spectroscopy
- Publication
Angewandte Chemie, 2019, Vol 131, Issue 28, p9499
- ISSN
0044-8249
- Publication type
Article
- DOI
10.1002/ange.201902852