UNIT 1.21 Overview of Receptor Allosterism

  1. Arthur Christopoulos

Published Online: 1 MAY 2001

DOI: 10.1002/0471141755.ph0121s11

Current Protocols in Pharmacology

Current Protocols in Pharmacology

How to Cite

Christopoulos, A. 2001. Overview of Receptor Allosterism. Current Protocols in Pharmacology. 11:1.21:1.21.1–1.21.45.

Author Information

  1. University of Melbourne, Victoria, Australia

Publication History

  1. Published Online: 1 MAY 2001
  2. Published Print: DEC 2000

This is not the most recent version of the article. View current version (1 DEC 2010)


Studies of the behavior of many ligand-gated ion channels have long provided evidence that more than one molecule of ligand was able to bind to each receptor complex, a phenomenon termed cooperativity. The conclusion that some receptors possessed more than one binding site for ligands thus invoked another phenomenon that was originally described in the field of enzymology, that is, the concept of allosteric binding sites. The biological activity of enzymes can be modified, either in a positive or negative fashion, by the binding of ligands to sites that are topographically distinct from the substrate-binding site. These accessory binding sites are termed allosteric sites, in contrast to the substrate-binding (active) site (the isosteric site). Thus, allosteric interactions arise because the binding of a ligand to the allosteric site induces a conformational change in the protein that modulates the binding of the substrate to the isosteric site, and vice versa. The biological activity of the enzyme arises from the subsequent (modified) properties of the substrate-binding site, and not through a direct effect of the allosteric modulator itself. This overview unit discusses definitions of various terms used in the field of receptor allosterism, and explains in clear terms how allosteric transitions and interactions can affect receptor activation. In addition, the functions of allosteric modulators are discussed along with explanations of how these modulators can be attractive tools for drug development.