Structural insight to mutation effects uncover a common allosteric site in class C GPCRs
Research output: Contribution to journal › Journal article › peer-review
Standard
Structural insight to mutation effects uncover a common allosteric site in class C GPCRs. / Harpsøe, Kasper; Boesgaard, Michael W; Munk, Christian; Bräuner-Osborne, Hans; Gloriam, David E.
In: Bioinformatics (Oxford, England), Vol. 33, No. 8, btw784, 2017, p. 1116-1120.Research output: Contribution to journal › Journal article › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Structural insight to mutation effects uncover a common allosteric site in class C GPCRs
AU - Harpsøe, Kasper
AU - Boesgaard, Michael W
AU - Munk, Christian
AU - Bräuner-Osborne, Hans
AU - Gloriam, David E
N1 - © The Author(s) 2016. Published by Oxford University Press.
PY - 2017
Y1 - 2017
N2 - 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.CONTACT: david.gloriam@sund.ku.dk SUPPLEMENTARY INFORMATION: Available at Bioinformatics online.
AB - 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.CONTACT: david.gloriam@sund.ku.dk SUPPLEMENTARY INFORMATION: Available at Bioinformatics online.
U2 - 10.1093/bioinformatics/btw784
DO - 10.1093/bioinformatics/btw784
M3 - Journal article
C2 - 28011766
VL - 33
SP - 1116
EP - 1120
JO - Computer Applications in the Biosciences
JF - Computer Applications in the Biosciences
SN - 1471-2105
IS - 8
M1 - btw784
ER -
ID: 170677847