+Open data
-Basic information
Entry | Database: PDB / ID: 6y1z | ||||||||||||
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Title | Mouse serotonin 5HT3 receptor in complex with palonosetron | ||||||||||||
Components | 5-hydroxytryptamine receptor 3A | ||||||||||||
Keywords | TRANSPORT PROTEIN / Receptor / Pentameric ligand-gated ion channel / antiemetic | ||||||||||||
Function / homology | Function and homology information Neurotransmitter receptors and postsynaptic signal transmission / serotonin-gated monoatomic cation channel activity / serotonin-activated cation-selective channel complex / serotonin receptor signaling pathway / excitatory extracellular ligand-gated monoatomic ion channel activity / serotonin binding / inorganic cation transmembrane transport / acetylcholine-gated monoatomic cation-selective channel activity / cleavage furrow / transmembrane transporter complex ...Neurotransmitter receptors and postsynaptic signal transmission / serotonin-gated monoatomic cation channel activity / serotonin-activated cation-selective channel complex / serotonin receptor signaling pathway / excitatory extracellular ligand-gated monoatomic ion channel activity / serotonin binding / inorganic cation transmembrane transport / acetylcholine-gated monoatomic cation-selective channel activity / cleavage furrow / transmembrane transporter complex / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / presynaptic membrane / postsynaptic membrane / neuron projection / axon / neuronal cell body / glutamatergic synapse / synapse / identical protein binding / plasma membrane Similarity search - Function | ||||||||||||
Biological species | Mus musculus (house mouse) | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.82 Å | ||||||||||||
Authors | Zarkadas, E. / Perot, J. / Nury, H. | ||||||||||||
Funding support | France, 1items
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Citation | Journal: Structure / Year: 2020 Title: The Binding of Palonosetron and Other Antiemetic Drugs to the Serotonin 5-HT3 Receptor. Authors: Eleftherios Zarkadas / Hong Zhang / Wensheng Cai / Gregory Effantin / Jonathan Perot / Jacques Neyton / Christophe Chipot / Guy Schoehn / Francois Dehez / Hugues Nury / 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 ...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. | ||||||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6y1z.cif.gz | 374.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6y1z.ent.gz | 306.7 KB | Display | PDB format |
PDBx/mmJSON format | 6y1z.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6y1z_validation.pdf.gz | 2 MB | Display | wwPDB validaton report |
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Full document | 6y1z_full_validation.pdf.gz | 2 MB | Display | |
Data in XML | 6y1z_validation.xml.gz | 55 KB | Display | |
Data in CIF | 6y1z_validation.cif.gz | 80.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/y1/6y1z ftp://data.pdbj.org/pub/pdb/validation_reports/y1/6y1z | HTTPS FTP |
-Related structure data
Related structure data | 10673MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Protein , 1 types, 5 molecules ADBCE
#1: Protein | Mass: 63682.719 Da / Num. of mol.: 5 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Gene: Htr3a, 5ht3, Htr3 / Production host: Homo sapiens (human) / References: UniProt: P23979 |
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-Sugars , 3 types, 15 molecules
#2: Polysaccharide | beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #3: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #6: Sugar | ChemComp-NAG / |
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-Non-polymers , 3 types, 15 molecules
#4: Chemical | ChemComp-TRP / #5: Chemical | ChemComp-HIS / #7: Chemical | ChemComp-O7B / ( |
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-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Mouse serotonin 5-HT3 receptor in complex with palonosetron Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
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Source (natural) | Organism: Mus musculus (house mouse) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 53 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.17.1_3660: / Classification: refinement | ||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Symmetry | Point symmetry: C5 (5 fold cyclic) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.82 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 127971 / Symmetry type: POINT | ||||||||||||||||||||||||
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