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Mouse serotonin 5HT3 receptor in complex with palonosetronMouse serotonin 5HT3 receptor in complex with palonosetron
Structural highlights
Function5HT3A_MOUSE This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor is a ligand-gated ion channel, which when activated causes fast, depolarizing responses in neurons. It is a cation-specific, but otherwise relatively nonselective, ion channel. Publication Abstract from PubMedInaccurately perceived as niche drugs, antiemetics are key elements of cancer treatment alleviating the most dreaded side effect of chemotherapy. Serotonin 5-HT3 receptor antagonists are the most commonly prescribed class of drugs to control chemotherapy-induced nausea and vomiting. These antagonists have been clinically successful drugs since the 1980s, yet our understanding of how they operate at the molecular level has been hampered by the difficulty of obtaining structures of drug-receptor complexes. Here, we report the cryoelectron microscopy structure of the palonosetron-bound 5-HT3 receptor. We investigate the binding of palonosetron, granisetron, dolasetron, ondansetron, and cilansetron using molecular dynamics, covering the whole set of antagonists used in clinical practice. The structural and computational results yield detailed atomic insight into the binding modes of the drugs. In light of our data, we establish a comprehensive framework underlying the inhibition mechanism by the -setron drug family. The Binding of Palonosetron and Other Antiemetic Drugs to the Serotonin 5-HT3 Receptor.,Zarkadas E, Zhang H, Cai W, Effantin G, Perot J, Neyton J, Chipot C, Schoehn G, Dehez F, Nury H Structure. 2020 Jul 27. pii: S0969-2126(20)30237-9. doi:, 10.1016/j.str.2020.07.004. PMID:32726573[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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