Towards high throughput GPCR crystallography: In Meso soaking of Adenosine A2A Receptor crystals

Here we report an efficient method to generate multiple co-structures of the A 2A G protein-coupled receptor (GPCR) with small-molecules from a single preparation of a thermostabilised receptor crystallised in Lipidic Cubic Phase (LCP). Receptor crystallisation is achieved following purification usi...

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Bibliographic Details
Published in:Scientific reports 2018-01, Vol.8 (1), p.1-41, Article 41
Main Authors: Rucktooa, Prakash, Cheng, Robert K. Y., Segala, Elena, Geng, Tian, Errey, James C., Brown, Giles A., Cooke, Robert M., Marshall, Fiona H., Doré, Andrew S.
Format: Article
Language:English
Subjects:
631/154
631/535/1266
82
Affinity
Crystallography
Crystals
G protein-coupled receptors
Humanities and Social Sciences
Ligands
multidisciplinary
Science
Science (multidisciplinary)
Theophylline
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Summary:Here we report an efficient method to generate multiple co-structures of the A 2A G protein-coupled receptor (GPCR) with small-molecules from a single preparation of a thermostabilised receptor crystallised in Lipidic Cubic Phase (LCP). Receptor crystallisation is achieved following purification using a low affinity “carrier” ligand (theophylline) and crystals are then soaked in solutions containing the desired (higher affinity) compounds. Complete datasets to high resolution can then be collected from single crystals and seven structures are reported here of which three are novel. The method significantly improves structural throughput for ligand screening using stabilised GPCRs, thereby actively driving Structure-Based Drug Discovery (SBDD).
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-017-18570-w