TY - JOUR
T1 - Overview of receptor allosterism
AU - Gregory, Karen
AU - Sexton, Patrick
AU - Christopoulos, Arthur
PY - 2010/12
Y1 - 2010/12
N2 - In addition to the orthosteric site, which recognizes endogenous ligands, most G protein-coupled receptors (GPCRs) possess topographically distinct allosteric sites that can be recognized by small molecules and accessory cellular proteins. Ligand binding to allosteric sites promotes a conformational change in the GPCR that can alter orthosteric ligand affinity and/or efficacy. Moreover, there has been an increase in recent years in the identification of allosteric agonists that can directly activate the receptor in the absence of orthosteric ligand. Allosteric sites are attractive therapeutic targets because they can be exploited to achieve modes of selectivity and signaling that are not attainable by orthosteric means. However, an important challenge in this field remains the quantification of the myriad of possible allosteric effects on binding and signaling events. This unit provides an overview on GPCR allosterism and the different pharmacological approaches to understanding allosteric behaviors. © 2010 by John Wiley & Sons, Inc.
AB - In addition to the orthosteric site, which recognizes endogenous ligands, most G protein-coupled receptors (GPCRs) possess topographically distinct allosteric sites that can be recognized by small molecules and accessory cellular proteins. Ligand binding to allosteric sites promotes a conformational change in the GPCR that can alter orthosteric ligand affinity and/or efficacy. Moreover, there has been an increase in recent years in the identification of allosteric agonists that can directly activate the receptor in the absence of orthosteric ligand. Allosteric sites are attractive therapeutic targets because they can be exploited to achieve modes of selectivity and signaling that are not attainable by orthosteric means. However, an important challenge in this field remains the quantification of the myriad of possible allosteric effects on binding and signaling events. This unit provides an overview on GPCR allosterism and the different pharmacological approaches to understanding allosteric behaviors. © 2010 by John Wiley & Sons, Inc.
UR - http://www.scopus.com/inward/record.url?scp=84857488876&partnerID=8YFLogxK
U2 - 10.1002/0471141755.ph0121s51
DO - 10.1002/0471141755.ph0121s51
M3 - Article
C2 - 21935895
SN - 1934-8282
VL - Chapter 1
SP - 1.21-1 - 1.21-34
JO - Current Protocols in Pharmacology
JF - Current Protocols in Pharmacology
IS - Supp 51
ER -