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

October 5, 2017

Rucktooa, P., Cheng, R., Segala, E., et al.

Scientific Reports 2018, vol: 8(41) 10.1038/s41598-017-18570-w

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).

View Publication

Topics: Prometheus, nanoDSF, Membrane Proteins, Publications

Previous Article
Structural basis of species-selective antagonist binding to the succinate receptor
Structural basis of species-selective antagonist binding to the succinate receptor

Up next
Studying the interaction of membrane enzyme PgIB with substrate and inhibitory peptide
Studying the interaction of membrane enzyme PgIB with substrate and inhibitory peptide

Working with tricky membrane proteins?

NanoTemper tools can help

Find out how