Structures of G protein-coupled receptors reveal new opportunities for drug discovery
Robert M Cooke1, Alastair J H Brown1, Fiona H Marshall1
1Heptares Therapeutics, Biopark, Broadwater Road, Welwyn Garden City, Hertfordshire AL7 3AX, UK.
Abstract:
X-ray structures of G protein-coupled receptors (GPCRs) have now been reported for more than 60 ligands and 20 receptors, including examples from GPCR classes A, B, C and F. The new structures show previously unobtainable details of interactions between GPCRs and ligands, including the roles of lipophilic regions and water molecules as key drivers of binding. In addition, the structures have revealed several surprising ligand-binding modes, including sites outside the orthosteric pocket. This new information is dramatically changing the way we approach GPCR drug discovery.
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