Allosteric modulator

As an allosteric modulator, a substance referred to in the biochemistry and pharmacology, which changes the effects of an orthosteric ligand, such as an agonist or an inverse agonist to a target protein, typically a receptor ( modulated). Allosteric modulators bind to a different ( allosteric ) binding site than the orthosteric agonist binding site. They lead to a conformational change of the receptor protein, thereby changing the receptor affinity or activity of the orthosteric ligand. The positive allosteric modulator (PAM ) will result in a gain of negative allosteric modulator ( NAM) to weaken the effects of an agonist or inverse agonist, without itself, i.e. in the absence of an agonist or inverse agonist, to show an effect. Substances that occupy the allosteric binding site, but behave functionally neutral are called silent modulators ( SAM). Known allosteric modulators are the benzodiazepines, which increase the activity of the GABA receptor.

To be distinguished from the allosteric modulators are agonists which are able to activate in the absence of orthosteric ligand to a receptor by binding to an allosteric binding site immediately. Further, there is AGO allosteric modulators, allosteric agonists, which act both as (activators ), as well as allosteric modulators.

In the English literature the terms on-target and off-target binding site of the allosterism classified and indicates whether a protein binds to the same modulator as the orthosteric ligand, or whether it binds to a partner protein, as in GPCR oligomers occurs.