Towards high throughput GPCR crystallography: In Meso soaking of Adenosine A2A Receptor crystals.
Sci Rep
; 8(1): 41, 2018 01 08.
Article
de En
| MEDLINE
| ID: mdl-29311713
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).
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Récepteurs couplés aux protéines G
/
Récepteur A2A à l'adénosine
Limites:
Humans
Langue:
En
Journal:
Sci Rep
Année:
2018
Type de document:
Article
Pays d'affiliation:
Royaume-Uni