Conservation of Allosteric Ligand Binding Sites in G-Protein Coupled Receptors.

ABSTRACT: Despite the growing number of G protein-coupled receptor (GPCR) structures, only 39 structures have been cocrystallized with allosteric inhibitors. These structures have been studied by protein mapping using the FTMap server, which determines the clustering of small organic probe molecules distributed on the protein surface. The method has found druggable sites overlapping with the cocrystallized allosteric ligands in 21 GPCR structures. Mapping of Alphafold2 generated models of these proteins confirms that the same sites can be identified without the presence of bound ligands. We then mapped the 394 GPCR X-ray structures available at the time of the analysis (September 2020). Results show that for each of the 21 structures with bound ligands there exist many other GPCRs that have a strong

SUBMITTER: Wakefield AE 

PROVIDER: S-EPMC9847135 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature