RT Journal Article
SR Electronic
T1 Seven Transmembrane Receptors as Nature's Prototype Allosteric Protein: De-emphasizing the Geography of Binding
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 541
OP 543
DO 10.1124/mol.108.050062
VO 74
IS 3
A1 Terry P. Kenakin
YR 2008
UL http://molpharm.aspetjournals.org/content/74/3/541.abstract
AB The article in this issue by Redka et al. (p. 834) illustrates some interesting interactions between classified orthosteric (bind to the same recognition site as endogenous agonist) and allosteric (bind to a different site) ligands. Of particular interest are the methods used to deal with an obfuscating factor in these kinds of studies, namely the propensity of seven transmembrane receptors to form dimers and thus demonstrate allosteric effects through binding at the orthosteric site. The judicious use of kinetics to detect and quantify allosteric action also is demonstrated. The various unique properties of allosteric modulators are discussed in the context of the increasing prevalence of allosteric ligands as investigational drugs.