{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T06:40:30Z","timestamp":1790664030651,"version":"4.1.0"},"reference-count":78,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2020,10,16]],"date-time":"2020-10-16T00:00:00Z","timestamp":1602806400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,10,16]],"date-time":"2020-10-16T00:00:00Z","timestamp":1602806400000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,10,16]],"date-time":"2020-10-16T00:00:00Z","timestamp":1602806400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01GM108921"],"award-info":[{"award-number":["R01GM108921"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["17POST33671152"],"award-info":[{"award-number":["17POST33671152"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["20POST35210394"],"award-info":[{"award-number":["20POST35210394"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35GM134896"],"award-info":[{"award-number":["R35GM134896"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01GM131216"],"award-info":[{"award-number":["R01GM131216"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    Serotonin receptors (5-HT\n                    <jats:sub>3A<\/jats:sub>\n                    R) 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\n                    <jats:sub>3A<\/jats:sub>\n                    R 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\n                    <jats:sub>3A<\/jats:sub>\n                    R, the study reveals a distinct interaction fingerprint between the various setrons and binding-pocket residues that may underlie their diverse affinities. In addition, varying degrees of conformational change in the setron-5-HT\n                    <jats:sub>3A<\/jats:sub>\n                    R structures, throughout the channel and particularly along the channel activation pathway, suggests a novel mechanism of competitive inhibition.\n                  <\/jats:p>","DOI":"10.7554\/elife.57870","type":"journal-article","created":{"date-parts":[[2020,10,16]],"date-time":"2020-10-16T08:00:38Z","timestamp":1602835238000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.57870","source":"Crossref","is-referenced-by-count":52,"title":["High-resolution structures of multiple 5-HT3AR-setron complexes reveal a novel mechanism of competitive inhibition"],"prefix":"10.7554","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4018-8020","authenticated-orcid":true,"given":"Sandip","family":"Basak","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, United 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