Glossary of Pharmacology 

Allosteric Site

An allosteric site is a binding site on an enzyme or receptor that is distinct from the enzyme’s active site or receptor’s orthosteric site. The binding of molecules to the allosteric site in a receptor can enhance or diminish its activity without competing with the endogenous agonist for the orthosteric binding site. The allosteric site provides a mechanism by which molecules can regulate receptor activity.  

Image: An allosteric inhibitor binds to a separate area from the active site called an allosteric site. After binding, the inhibitor will change the shape of the active site, a conformational change, preventing the substrate from binding. 

The allosteric site is important for differential regulation of enzymes and receptors, such as non-competitive inhibition and signalling alteration such as biased signalling. In enzymes, this mechanism works by inhibitors binding to the allosteric site which inactivates the enzyme and therefore reduces product formation. Moreover, binding to the allosteric site means that increasing substrate concentration does not increase the rate of the reaction. In receptors, the binding of a ligand to an allosteric site may alter the activity of this receptor or affinity of the receptor for its orthosteric ligand. For example, G Protein-Coupled Receptors (GPCRs) are found to have allosteric sites in which ligands bind to modulate the activity of the receptor. 

Teaching Tips:  

https://www.youtube.com/watch?v=pZpZUqX10WE  

Linked terms:  Ligand, Substrate, Transmembrane receptor, GPCRs, Enzyme, Non-competitive inhibition, Conformational change 

Resources:  

Deodhar, M., Al Rihani, S. B., Arwood, M. J., Darakjian, L., Dow, P., Turgeon, J., & Michaud, V. (2020). Mechanisms of CYP450 Inhibition: Understanding Drug-Drug Interactions Due to Mechanism-Based Inhibition in Clinical Practice. Pharmaceutics, 12(9), 846. https://doi.org/10.3390/pharmaceutics12090846  

Delaune, K. P. (2022, September 12). Physiology, Noncompetitive Inhibitor. StatPearls - NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK545242/   

Wakefield, A. E., Bajusz, D., Kozakov, D., Keserű, G. M., & Vajda, S. (2022). Conservation of Allosteric Ligand Binding Sites in G-Protein Coupled Receptors. Journal of chemical information and modeling, 62(20), 4937–4954. https://doi.org/10.1021/acs.jcim.2c00209   

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