Preferential binding of allosteric modulators to active and inactive conformational states of metabotropic glutamate receptors.

ABSTRACT: Metabotropic glutamate receptors (mGluRs) are G protein coupled receptors that play important roles in synaptic plasticity and other neuro-physiological and pathological processes. Allosteric mGluR ligands are particularly promising drug targets because of their modulatory effects--enhancing or suppressing the response of mGluRs to glutamate. The mechanism by which this modulation occurs is not known. Here, we propose the hypothesis that positive and negative modulators will differentially stabilize the active and inactive conformations of the receptors, respectively. To test this hypothesis, we have generated computational models of the transmembrane regions of different mGluR subtypes in two different conformations. The inactive conformation was modeled using the crystal structure of the

SUBMITTER: Yanamala N 

PROVIDER: S-EPMC2259417 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature