High-resolution structures of multiple 5-HT_3AR-setron complexes reveal a novel mechanism of competitive inhibition.

ABSTRACT: Serotonin receptors (5-HT_3AR) play a crucial role in regulating gut movement, and are the principal target of setrons, a class of high-affinity competitive antagonists, used in the management of nausea and vomiting associated with radiation and chemotherapies. Structural insights into setron-binding poses and their inhibitory mechanisms are just beginning to emerge. Here, we present high-resolution cryo-EM structures of full-length 5-HT_3AR in complex with palonosetron, ondansetron, and alosetron. Molecular dynamic simulations of these structures embedded in a fully-hydrated lipid environment assessed the stability of ligand-binding poses and drug-target interactions over time. Together with simulation results of apo- and serotonin-bound 5-HT_3AR, the study r

SUBMITTER: Basak S 

PROVIDER: S-EPMC7655109 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature