6Y1Z

Mouse serotonin 5HT3 receptor in complex with palonosetron

Summary for 6Y1Z

• Entry DOI: 10.2210/pdb6y1z/pdb
• EMDB information: 10673
• Descriptor: 5-hydroxytryptamine receptor 3A, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• Functional Keywords: receptor, pentameric ligand-gated ion channel, antiemetic, transport protein
• Biological source: Mus musculus (house mouse)
• Total number of polymer chains: 5
• Total formula weight: 327858.32

Authors

Zarkadas, E.,Perot, J.,Nury, H. (deposition date: 2020-02-14, release date: 2020-03-04, Last modification date: 2024-11-06)

Primary citation

Zarkadas, E.,Zhang, H.,Cai, W.,Effantin, G.,Perot, J.,Neyton, J.,Chipot, C.,Schoehn, G.,Dehez, F.,Nury, H.
The Binding of Palonosetron and Other Antiemetic Drugs to the Serotonin 5-HT3 Receptor.
Structure, 28:1131-1140.e4, 2020

PubMed Abstract: Inaccurately 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.

PubMed: 32726573
DOI: 10.1016/j.str.2020.07.004

Experimental method

ELECTRON MICROSCOPY (2.82 Å)