Figure 2.
Allosteric modulation of GPCRs. The orthosteric site of a GPCR is the site where the endogenous ligand (brown) binds. Sites that are topographically distinct from the orthosteric site are known as allosteric sites. Ligands that bind to allosteric sites (red) can potentiate (PAMs) or depress (NAMs) orthosteric ligand affinity and efficacy. The simulated concentration response curves show the effect of increasing concentrations of PAMs (green lines) or NAMs (red lines) on the response to a GPCR agonist (black line).