Allosteric modulator

In biochemistry and pharmacology, an allosteric modulator is a substance which indirectly influences (modulates) the effects of an agonist or inverse agonist at a target protein, for example a receptor. Allosteric modulators bind to a site distinct from that of the orthosteric agonist binding site. Usually they induce a conformational change within the protein structure. A positive allosteric modulator (PAM) induces an amplification, a negative modulator (NAM) an attenuation of the effects of the orthosteric ligand without triggering a functional activity on its own in the absence of the orthosteric ligand. Substances that occupy the allosteric binding site and behave functionally neutral are called silent allosteric modulators (SAMs). Classic benzodiazepines are well-known PAMs.

From modulators the allosteric agonists are to be distinguished. They are able to directly activate a receptor via an allosteric binding site in the absence of an orthosteric ligand.

An ago-allosteric modulator both activates and modulates a receptor allosterically.

See also

• Allosteric regulation

References

• J. Monod, J. Wyman, J.P. Changeux (May 1965). "On the nature of allosteric transitions: A plausible model". Journal of Molecular Biology 12 (1): 88–118. doi:10.1016/S0022-2836(65)80285-6. PMID 14343300.