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Sci Rep. 2018 Jan 8;8(1):41. doi: 10.1038/s41598-017-18570-w.

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

Author information

1
Heptares Therapeutics Ltd, BioPark, Broadwater Road, Welwyn Garden City, Hertfordshire, AL7 3AX, UK.
2
LeadXpro, Park InnovAARE, 5232, Villigen, Switzerland.
3
Heptares Therapeutics Ltd, BioPark, Broadwater Road, Welwyn Garden City, Hertfordshire, AL7 3AX, UK. fiona.marshall@heptares.com.

Abstract

Here we report an efficient method to generate multiple co-structures of the A2A 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).

PMID:
29311713
PMCID:
PMC5758569
DOI:
10.1038/s41598-017-18570-w
[Indexed for MEDLINE]
Free PMC Article

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