From G Protein-coupled Receptor Structure Resolution to Rational Drug Design

A number of recent technical solutions have led to significant advances in G protein-coupled receptor (GPCR) structural biology. Apart from a detailed mechanistic view of receptor activation, the new structures have revealed novel ligand binding sites. Together, these insights provide avenues for ra...

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Bibliographic Details
Published in:The Journal of biological chemistry 2015-08, Vol.290 (32), p.19489-19495
Main Authors: Jazayeri, Ali, Dias, Joao M., Marshall, Fiona H.
Format: Article
Language:English
Subjects:
Allosteric Regulation
Allosteric Site - drug effects
Computer-Aided Design
Crystallography, X-Ray - methods
Drug Design
drug discovery
G protein-coupled receptor (GPCR)
Humans
Ligands
membrane protein
Minireviews
Models, Molecular
Protein Binding
Protein Structure, Secondary
Protein Structure, Tertiary
Receptors, G-Protein-Coupled - agonists
Receptors, G-Protein-Coupled - antagonists & inhibitors
Receptors, G-Protein-Coupled - genetics
Receptors, G-Protein-Coupled - metabolism
Small Molecule Libraries - chemical synthesis
Small Molecule Libraries - chemistry
Small Molecule Libraries - pharmacology
Structure-Activity Relationship
X-ray crystallography
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Summary:A number of recent technical solutions have led to significant advances in G protein-coupled receptor (GPCR) structural biology. Apart from a detailed mechanistic view of receptor activation, the new structures have revealed novel ligand binding sites. Together, these insights provide avenues for rational drug design to modulate the activities of these important drug targets. The application of structural data to GPCR drug discovery ushers in an exciting era with the potential to improve existing drugs and discover new ones. In this review, we focus on technical solutions that have accelerated GPCR crystallography as well as some of the salient findings from structures that are relevant to drug discovery. Finally, we outline some of the approaches used in GPCR structure based drug design.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.R115.668251