Ligand selectivity hotspots in serotonin GPCRs.
Trends Pharmacol Sci
; 44(12): 978-990, 2023 12.
Article
em En
| MEDLINE
| ID: mdl-37914598
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores Acoplados a Proteínas G
/
Transtornos de Enxaqueca
Limite:
Humans
Idioma:
En
Revista:
Trends Pharmacol Sci
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Dinamarca