Ligand selectivity hotspots in serotonin GPCRs

Department of Drug Design and Pharmacology

Ligand selectivity hotspots in serotonin GPCRs

Research output: Contribution to journal › Review › Research › peer-review

Standard

Ligand selectivity hotspots in serotonin GPCRs. / Simon, Icaro A; Bjørn-Yoshimoto, Walden E; Harpsøe, Kasper; Iliadis, Stylianos; Svensson, Bo; Jensen, Anders A; Gloriam, David E.

In: Trends in Pharmacological Sciences, Vol. 44, No. 12, 2023, p. 978-990.

Research output: Contribution to journal › Review › Research › peer-review

Harvard

Simon, IA, Bjørn-Yoshimoto, WE, Harpsøe, K, Iliadis, S, Svensson, B, Jensen, AA & Gloriam, DE 2023, 'Ligand selectivity hotspots in serotonin GPCRs', Trends in Pharmacological Sciences, vol. 44, no. 12, pp. 978-990. https://doi.org/10.1016/j.tips.2023.09.012

APA

Simon, I. A., Bjørn-Yoshimoto, W. E., Harpsøe, K., Iliadis, S., Svensson, B., Jensen, A. A., & Gloriam, D. E. (2023). Ligand selectivity hotspots in serotonin GPCRs. Trends in Pharmacological Sciences, 44(12), 978-990. https://doi.org/10.1016/j.tips.2023.09.012

Vancouver

Simon IA, Bjørn-Yoshimoto WE, Harpsøe K, Iliadis S, Svensson B, Jensen AA et al. Ligand selectivity hotspots in serotonin GPCRs. Trends in Pharmacological Sciences. 2023;44(12):978-990. https://doi.org/10.1016/j.tips.2023.09.012

Author

Simon, Icaro A ; Bjørn-Yoshimoto, Walden E ; Harpsøe, Kasper ; Iliadis, Stylianos ; Svensson, Bo ; Jensen, Anders A ; Gloriam, David E. / Ligand selectivity hotspots in serotonin GPCRs. In: Trends in Pharmacological Sciences. 2023 ; Vol. 44, No. 12. pp. 978-990.

Bibtex

@article{ccbd0f0bb37a4d89b56946fdec9aaa40,

title = "Ligand selectivity hotspots in serotonin GPCRs",

abstract = "Serotonin is a neurotransmitter regulating numerous physiological processes also modulated by drugs, for example, schizophrenia, depression, migraine, and obesity. However, these drugs typically have adverse effects caused by promiscuous binding across 12 serotonin and more than 20 homologous receptors. Recently, structures of the entire serotonin receptor family uncovered molecular ligand recognition. Here, we present a map of 19 'selectivity hotspots', that is, nonconserved binding site residues governing selectivity via favorable target interactions or repulsive 'off-target' contacts. Furthermore, we review functional rationale from observed ligand-binding affinities and mutagenesis effects. Unifying knowledge underlying specific probes and drugs is critical toward the functional characterization of different receptors and alleviation of adverse effects.",

author = "Simon, {Icaro A} and Bj{\o}rn-Yoshimoto, {Walden E} and Kasper Harps{\o}e and Stylianos Iliadis and Bo Svensson and Jensen, {Anders A} and Gloriam, {David E}",

year = "2023",

doi = "10.1016/j.tips.2023.09.012",

language = "English",

volume = "44",

pages = "978--990",

journal = "Trends in Pharmacological Sciences",

issn = "0165-6147",

publisher = "Elsevier Ltd. * Trends Journals",

number = "12",

}

RIS

TY - JOUR

T1 - Ligand selectivity hotspots in serotonin GPCRs

AU - Simon, Icaro A

AU - Bjørn-Yoshimoto, Walden E

AU - Harpsøe, Kasper

AU - Iliadis, Stylianos

AU - Svensson, Bo

AU - Jensen, Anders A

AU - Gloriam, David E

PY - 2023

Y1 - 2023

N2 - Serotonin is a neurotransmitter regulating numerous physiological processes also modulated by drugs, for example, schizophrenia, depression, migraine, and obesity. However, these drugs typically have adverse effects caused by promiscuous binding across 12 serotonin and more than 20 homologous receptors. Recently, structures of the entire serotonin receptor family uncovered molecular ligand recognition. Here, we present a map of 19 'selectivity hotspots', that is, nonconserved binding site residues governing selectivity via favorable target interactions or repulsive 'off-target' contacts. Furthermore, we review functional rationale from observed ligand-binding affinities and mutagenesis effects. Unifying knowledge underlying specific probes and drugs is critical toward the functional characterization of different receptors and alleviation of adverse effects.

AB - Serotonin is a neurotransmitter regulating numerous physiological processes also modulated by drugs, for example, schizophrenia, depression, migraine, and obesity. However, these drugs typically have adverse effects caused by promiscuous binding across 12 serotonin and more than 20 homologous receptors. Recently, structures of the entire serotonin receptor family uncovered molecular ligand recognition. Here, we present a map of 19 'selectivity hotspots', that is, nonconserved binding site residues governing selectivity via favorable target interactions or repulsive 'off-target' contacts. Furthermore, we review functional rationale from observed ligand-binding affinities and mutagenesis effects. Unifying knowledge underlying specific probes and drugs is critical toward the functional characterization of different receptors and alleviation of adverse effects.

U2 - 10.1016/j.tips.2023.09.012

DO - 10.1016/j.tips.2023.09.012

M3 - Review

C2 - 37914598

VL - 44

SP - 978

EP - 990

JO - Trends in Pharmacological Sciences

JF - Trends in Pharmacological Sciences

SN - 0165-6147

IS - 12

ER -

ID: 371617151