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. Author manuscript; available in PMC: 2019 Sep 25.
Published in final edited form as: Curr Top Med Chem. 2019;19(16):1381–1398. doi: 10.2174/1568026619666190709101449

Fig. (7). A schematic presentation of potential allosteric modulation of GPCR signal transduction is depicted.

Fig. (7).

The allosteric ligand binds to a site (orange circle) that is distinctly different than the orthosteric site (blue circle) which accommodates the orthosteric ligand. Actual binding site locations are generally dictated by the specific GPCR family member. Allosteric modulators can modulate binding affinity (α) and/or efficacy (β) of orthosteric ligands in a positive (PAM) or negative manner (NAM), or may simply occupy the site as a neutral allosteric ligand (NAL). The nature of the modulation is determined by several features of signaling including the orthosteric ligand employed (i.e., probe dependence) as well as the ligand-dependent selectivity for certain downstream transduction mechanisms within a given cell (i.e., biased signaling).