+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-10673 | |||||||||
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Title | Mouse serotonin 5HT3 receptor in complex with palonosetron | |||||||||
Map data | Mouse serotonin 5HT3 receptor bound to palonosetron | |||||||||
Sample |
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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 | single particle reconstruction / cryo EM / Resolution: 2.82 Å | |||||||||
Authors | Zarkadas E / Perot J / Nury H | |||||||||
Funding support | France, 1 items
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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 | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_10673.map.gz | 47.9 MB | EMDB map data format | |
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Header (meta data) | emd-10673-v30.xml emd-10673.xml | 11.9 KB 11.9 KB | Display Display | EMDB header |
Images | emd_10673.png | 146.6 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-10673 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-10673 | HTTPS FTP |
-Validation report
Summary document | emd_10673_validation.pdf.gz | 429.1 KB | Display | EMDB validaton report |
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Full document | emd_10673_full_validation.pdf.gz | 428.7 KB | Display | |
Data in XML | emd_10673_validation.xml.gz | 6.2 KB | Display | |
Data in CIF | emd_10673_validation.cif.gz | 7 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-10673 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-10673 | HTTPS FTP |
-Related structure data
Related structure data | 6y1zMC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_10673.map.gz / Format: CCP4 / Size: 52.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Mouse serotonin 5HT3 receptor bound to palonosetron | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.067 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : Mouse serotonin 5-HT3 receptor in complex with palonosetron
Entire | Name: Mouse serotonin 5-HT3 receptor in complex with palonosetron |
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Components |
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-Supramolecule #1: Mouse serotonin 5-HT3 receptor in complex with palonosetron
Supramolecule | Name: Mouse serotonin 5-HT3 receptor in complex with palonosetron type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: Mus musculus (house mouse) |
Recombinant expression | Organism: Homo sapiens (human) |
-Macromolecule #1: 5-hydroxytryptamine receptor 3A
Macromolecule | Name: 5-hydroxytryptamine receptor 3A / type: protein_or_peptide / ID: 1 / Number of copies: 5 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 63.682719 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MRLCIPQVLL ALFLSMLTGP GEGSRRRWSH PQFEKGGGSG GGSGGGSWSH PQFEKGGGSG GGSGGGSWSH PQFEKGGGSG GGSGGGSWS HPQFEKENLY FQGSGATQAR DTTQPALLRL SDHLLANYKK GVRPVRDWRK PTTVSIDVIM YAILNVDEKN Q VLTTYIWY ...String: MRLCIPQVLL ALFLSMLTGP GEGSRRRWSH PQFEKGGGSG GGSGGGSWSH PQFEKGGGSG GGSGGGSWSH PQFEKGGGSG GGSGGGSWS HPQFEKENLY FQGSGATQAR DTTQPALLRL SDHLLANYKK GVRPVRDWRK PTTVSIDVIM YAILNVDEKN Q VLTTYIWY RQYWTDEFLQ WTPEDFDNVT KLSIPTDSIW VPDILINEFV DVGKSPNIPY VYVHHRGEVQ NYKPLQLVTA CS LDIYNFP FDVQNCSLTF TSWLHTIQDI NITLWRSPEE VRSDKSIFIN QGEWELLEVF PQFKEFSIDI SNSYAEMKFY VII RRRPLF YAVSLLLPSI FLMVVDIVGF CLPPDSGERV SFKITLLLGY SVFLIIVSDT LPATAIGTPL IGVYFVVCMA LLVI SLAET IFIVRLVHKQ DLQRPVPDWL RHLVLDRIAW ILCLGEQPMA HRPPATFQAN KTDDCSGSDL LPAMGNHCSH VGGPQ DLEK TPRGRGSPLP PPREASLAVR GLLQELSSIR HFLEKRDEMR EVARDWLRVG YVLDRLLFRI YLLAVLAYSI TLVTLW SIW HSS |
-Macromolecule #4: TRYPTOPHAN
Macromolecule | Name: TRYPTOPHAN / type: ligand / ID: 4 / Number of copies: 5 / Formula: TRP |
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Molecular weight | Theoretical: 204.225 Da |
Chemical component information | ChemComp-TRP: |
-Macromolecule #5: HISTIDINE
Macromolecule | Name: HISTIDINE / type: ligand / ID: 5 / Number of copies: 5 / Formula: HIS |
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Molecular weight | Theoretical: 156.162 Da |
Chemical component information | ChemComp-HIS: |
-Macromolecule #6: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 6 / Number of copies: 5 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-Macromolecule #7: (3~{a}~{S})-2-[(3~{S})-1-azabicyclo[2.2.2]octan-3-yl]-3~{a},4,5,6...
Macromolecule | Name: (3~{a}~{S})-2-[(3~{S})-1-azabicyclo[2.2.2]octan-3-yl]-3~{a},4,5,6-tetrahydro-3~{H}-benzo[de]isoquinolin-1-one type: ligand / ID: 7 / Number of copies: 5 / Formula: O7B |
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Molecular weight | Theoretical: 296.407 Da |
Chemical component information | ChemComp-O7B: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 53.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: EMDB MAP EMDB ID: |
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Final reconstruction | Applied symmetry - Point group: C5 (5 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 2.82 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. v2.13) / Number images used: 127971 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |