The Implication of the First Agonist Bound Activated GPCR X-ray Structure on GPCR in Silico Modeling.

ABSTRACT: The very recently published first X-ray structure of the β2 adrenergic receptor in its active state hosting a small molecule (PDB ID: 3P0G) reveals a lot of information about the G-protein-coupled receptor (GPCR) activation process from a structural point of view. When compared to the inactive state crystal structure of β2, large differences are seen in the GPCR helical structure at the cytoplasmatic side, whereas very subtle changes occur at the ligand binding site. The observation that there are hardly any differences in the binding site of agonists and inverse agonists implies that in silico predictions of the efficacy of ligands will be very hard. This is illustrated by the example of an already published binding mode of a β2 agonist, which has been modeled into the inactive state X-ra

SUBMITTER: Tautermann CS 

PROVIDER: S-EPMC4017970 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature