Towards high throughput GPCR crystallography: In Meso soaking of Adenosine A2A Receptor crystals
Rucktooa, P., Cheng R. et al. 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 A2A G protein-coupled receptor (GPCR) with small-mols. from a single preparation of a thermostabilized receptor crystallized in Lipidic Cubic Phase (LCP). Receptor crystallization 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 stabilized GPCRs, thereby actively driving Structure-Based Drug Discovery (SBDD).