title: Structures of G protein-coupled receptors reveal new opportunities for drug discovery.
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.
authors: Heptares Therapeutics, Biopark, Broadwater Road, Welwyn Garden City, Hertfordshire AL7 3AX, UK.
authors: Robert M
authors: RM
authors: Cooke
authors: Heptares Therapeutics, Biopark, Broadwater Road, Welwyn Garden City, Hertfordshire AL7 3AX, UK.
authors: Alastair J H
authors: AJ
authors: Brown
authors: Heptares Therapeutics, Biopark, Broadwater Road, Welwyn Garden City, Hertfordshire AL7 3AX, UK.
authors: Fiona H
authors: FH
authors: Marshall
authors: Heptares Therapeutics, Biopark, Broadwater Road, Welwyn Garden City, Hertfordshire AL7 3AX, UK. Electronic address: jon.mason@heptares.com.
authors: Jonathan S
authors: JS
authors: Mason
mesh_terms: D001665:Binding Sites; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D008024:Ligands; D011485:Protein Binding; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000378:metabolism
chemical_list: D008024:Ligands; D043562:Receptors, G-Protein-Coupled