Integrating structural and mutagenesis data to elucidate GPCR ligand binding

Christian Munk; Kasper Harpsøe; Alexander S Hauser; Vignir Isberg; David E Gloriam

doi:10.1016/j.coph.2016.07.003

Integrating structural and mutagenesis data to elucidate GPCR ligand binding

Christian Munk, Kasper Harpsøe, Alexander S Hauser, Vignir Isberg, David E Gloriam

Department of Drug Design and Pharmacology

27 Citations (Scopus)

Abstract

G protein-coupled receptors (GPCRs) represent the largest family of human membrane proteins, as well as drug targets. A recent boom in GPCR structural biology has provided detailed images of receptor ligand binding sites and interactions on the molecular level. An ever-increasing number of ligands is reported that exhibit activity through multiple receptors, binding in allosteric sites, and bias towards different intracellular signalling pathways. Furthermore, a wealth of single point mutants has accumulated in literature and public databases. Integrating these structural and mutagenesis data will help elucidate new GPCR ligand binding sites, and ultimately design drugs with tailored pharmacological activity.

Original language	English
Journal	Current Opinion in Pharmacology
Volume	30
Pages (from-to)	51-58
Number of pages	8
ISSN	1471-4892
DOIs	https://doi.org/10.1016/j.coph.2016.07.003
Publication status	Published - 1 Oct 2016

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AU - Isberg, Vignir

AU - Gloriam, David E

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N2 - G protein-coupled receptors (GPCRs) represent the largest family of human membrane proteins, as well as drug targets. A recent boom in GPCR structural biology has provided detailed images of receptor ligand binding sites and interactions on the molecular level. An ever-increasing number of ligands is reported that exhibit activity through multiple receptors, binding in allosteric sites, and bias towards different intracellular signalling pathways. Furthermore, a wealth of single point mutants has accumulated in literature and public databases. Integrating these structural and mutagenesis data will help elucidate new GPCR ligand binding sites, and ultimately design drugs with tailored pharmacological activity.

AB - G protein-coupled receptors (GPCRs) represent the largest family of human membrane proteins, as well as drug targets. A recent boom in GPCR structural biology has provided detailed images of receptor ligand binding sites and interactions on the molecular level. An ever-increasing number of ligands is reported that exhibit activity through multiple receptors, binding in allosteric sites, and bias towards different intracellular signalling pathways. Furthermore, a wealth of single point mutants has accumulated in literature and public databases. Integrating these structural and mutagenesis data will help elucidate new GPCR ligand binding sites, and ultimately design drugs with tailored pharmacological activity.

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DO - 10.1016/j.coph.2016.07.003

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Integrating structural and mutagenesis data to elucidate GPCR ligand binding

Abstract

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