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Structural insight to mutation effects uncover a common allosteric site in class C GPCRs
- Source :
- Harpsøe, K, Boesgaard, M W, Munk, C, Bräuner-Osborne, H & Gloriam, D E 2017, ' Structural insight to mutation effects uncover a common allosteric site in class C GPCRs ', Bioinformatics (Oxford, England), vol. 33, no. 8, btw784, pp. 1116-1120 . https://doi.org/10.1093/bioinformatics/btw784, Bioinformatics
- Publication Year :
- 2017
-
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 structures. Availability and Implementation All collated mutagenesis data is available in the GPCRdb mutation browser at http://gpcrdb.org/mutations/ and can be analyzed online or downloaded in excel format. Supplementary information Supplementary data are available at Bioinformatics online.
- Subjects :
- 0301 basic medicine
Statistics and Probability
Computer science
Receptor, Metabotropic Glutamate 5
Allosteric regulation
Protein domain
Mutagenesis (molecular biology technique)
Class C GPCR
Computational biology
Crystal structure
Ligands
Bioinformatics
medicine.disease_cause
Biochemistry
Protein Structure, Secondary
Receptors, G-Protein-Coupled
03 medical and health sciences
Protein structure
Allosteric Regulation
Protein Domains
medicine
Humans
Binding site
Discovery Notes
Receptor
Molecular Biology
Phylogeny
G protein-coupled receptor
chemistry.chemical_classification
Mutation
Binding Sites
Ligand
Mutagenesis
Rational design
Structural Bioinformatics
Computer Science Applications
Amino acid
Computational Mathematics
Transmembrane domain
030104 developmental biology
Computational Theory and Mathematics
chemistry
Mutagenesis, Site-Directed
Protein Multimerization
Allosteric Site
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Harpsøe, K, Boesgaard, M W, Munk, C, Bräuner-Osborne, H & Gloriam, D E 2017, ' Structural insight to mutation effects uncover a common allosteric site in class C GPCRs ', Bioinformatics (Oxford, England), vol. 33, no. 8, btw784, pp. 1116-1120 . https://doi.org/10.1093/bioinformatics/btw784, Bioinformatics
- Accession number :
- edsair.doi.dedup.....6b773476312e8ae7e8456fdc2ce037c5