Structural insight to mutation effects uncover a common allosteric site in class C GPCRs.

ABSTRACT:

Motivation

Class C G protein-coupled receptors (GPCRs) regulate important physiological functions and allosteric modulators binding to the transmembrane domain constitute an attractive and, due to a lack of structural insight, a virtually unexplored potential for therapeutics and the food industry. Combining pharmacological site-directed mutagenesis data with the recent class C GPCR experimental structures will provide a foundation for rational design of new therapeutics.

Results

We uncover one common site for both positive and negative modulators with different amino acid layouts that can be utilized to obtain selectivity. Additionally, we show a large potential for structure-based modulator design, especially for four orphan receptors with high similarity to the crystal st

SUBMITTER: Harpsoe K 

PROVIDER: S-EPMC5408886 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature