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

Research output: Contribution to journalJournal articleResearchpeer-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 journalJournal articleResearchpeer-review

Harvard

Harpsøe, K, Boesgaard, MW, Munk, C, Bräuner-Osborne, H & Gloriam, DE 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

APA

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), 33(8), 1116-1120. [btw784]. https://doi.org/10.1093/bioinformatics/btw784

Vancouver

Harpsøe K, Boesgaard MW, Munk C, Bräuner-Osborne H, Gloriam DE. Structural insight to mutation effects uncover a common allosteric site in class C GPCRs. Bioinformatics (Oxford, England). 2017;33(8):1116-1120. btw784. https://doi.org/10.1093/bioinformatics/btw784

Author

Harpsøe, Kasper ; Boesgaard, Michael W ; Munk, Christian ; Bräuner-Osborne, Hans ; Gloriam, David E. / Structural insight to mutation effects uncover a common allosteric site in class C GPCRs. In: Bioinformatics (Oxford, England). 2017 ; Vol. 33, No. 8. pp. 1116-1120.

Bibtex

@article{dbe0e4bc1253427bb760a8a762a1baf0,
title = "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 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.",
author = "Kasper Harps{\o}e and Boesgaard, {Michael W} and Christian Munk and Hans Br{\"a}uner-Osborne and Gloriam, {David E}",
note = "{\circledC} The Author(s) 2016. Published by Oxford University Press.",
year = "2017",
doi = "10.1093/bioinformatics/btw784",
language = "English",
volume = "33",
pages = "1116--1120",
journal = "Bioinformatics",
issn = "1367-4803",
publisher = "Oxford University Press",
number = "8",

}

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

VL - 33

SP - 1116

EP - 1120

JO - Bioinformatics

JF - Bioinformatics

SN - 1367-4803

IS - 8

M1 - btw784

ER -

ID: 170677847