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. 2021 Feb 10;22(4):1763. doi: 10.3390/ijms22041763

Figure 1.

Figure 1

Overview of different modes of allosteric modulation. Agonist dose–response curves in absence of an allosteric ligand are shown in orange, while presence of an allosteric ligand is depicted in blue. (A) A positive allosteric modulator (PAM) increases affinity and/or efficacy of an orthosteric ligand, and thus has positive co-operativity factors α and/or β. (B) A negative allosteric modulator (NAM) reduces affinity and/or efficacy of an orthosteric ligand and has a negative α- and/or β-factor. (C) An ago-PAM has intrinsic efficacy (τ > 0) and is also a PAM for an orthosteric ligand. (D) An ago-NAM is a negative allosteric modulator for an orthosteric ligand that increases the activity state of the receptor (τ > 0) itself. (E) A PAM-antagonist decreases efficacy of an orthosteric agonist and thus functions as an antagonist (β < 0) and simultaneously increases affinity of the orthosteric ligand (α > 0). (F) A negative allosteric ligand (NAL) or silent allosteric modulator (SAM) has no effect on the affinity or efficacy of an orthosteric ligand (α,β = 0) but occupies the allosteric binding site, and thus competes with other allosteric ligands for this site.