Novel Allosteric Modulators of G Protein-coupled Receptors

被引：157

作者：

Gentry, Patrick R. ^{[1
]}

Sexton, Patrick M. ^{[1
]}

Christopoulos, Arthur ^{[1
]}

机构：

[1] Monash Univ, Monash Inst Pharmaceut Sci, Drug Discovery Biol, Parkville, Vic 3052, Australia

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2015年 / 290卷 / 32期

基金：

英国医学研究理事会;

关键词：

MUSCARINIC ACETYLCHOLINE-RECEPTORS; METABOTROPIC GLUTAMATE RECEPTORS; IMPROVES GLYCEMIC CONTROL; DRUG DISCOVERY; BINDING-SITE; STRUCTURAL BASIS; IN-VIVO; FUNCTIONAL SELECTIVITY; MONOCLONAL-ANTIBODY; SIGNALING PATHWAYS;

D O I：

10.1074/jbc.R115.662759

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

G protein-coupled receptors (GPCRs) are allosteric proteins, because their signal transduction relies on interactions between topographically distinct, yet conformationally linked, domains. Much of the focus on GPCR allostery in the new millennium, however, has been on modes of targeting GPCR allosteric sites with chemical probes due to the potential for novel therapeutics. It is now apparent that some GPCRs possess more than one targetable allosteric site, in addition to a growing list of putative endogenous modulators. Advances in structural biology are also shedding new insights into mechanisms of allostery, although the complexities of candidate allosteric drugs necessitate rigorous biological characterization.

引用

收藏

页码：19478 / 19488

页数：11

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