Molecular mechanism of setron-mediated inhibition of full-length 5-HT_3A receptor.

ABSTRACT: Serotonin receptor (5-HT_3AR) is the most common therapeutic target to manage the nausea and vomiting during cancer therapies and in the treatment of irritable bowel syndrome. Setrons, a class of competitive antagonists, cause functional inhibition of 5-HT_3AR in the gastrointestinal tract and brainstem, acting as effective anti-emetic agents. Despite their prevalent use, the molecular mechanisms underlying setron binding and inhibition of 5-HT_3AR are not fully understood. Here, we present the structure of granisetron-bound full-length 5-HT_3AR solved by single-particle cryo-electron microscopy to 2.92 Å resolution. The reconstruction reveals the orientation of granisetron in the orthosteric site with unambiguous density for interacting sidechains.

SUBMITTER: Basak S 

PROVIDER: S-EPMC6642186 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature