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Publication - Dr Richard Sessions

    The Aminotriazole Antagonist Cmpd-1 Stabilises a Novel Inactive State of the Adenosine 2A Receptor

    Citation

    Landin, E, Lovera, S, Mercier, J, Fabritiis, Gd, Kelm, S, Sessions, R, Taylor, RJ, Sands, Z, Joedicke, L & Crump, M, 2019, ‘The Aminotriazole Antagonist Cmpd-1 Stabilises a Novel Inactive State of the Adenosine 2A Receptor’. Angewandte Chemie - International Edition.

    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.

    Full details in the University publications repository