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Open data
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Basic information
Entry | Database: PDB / ID: 8s9c | ||||||
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Title | Cryo-EM structure of Nav1.7 with CBZ | ||||||
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![]() | MEMBRANE PROTEIN / Cryo-EM / sodium channel / VGSC / Nav1.7 | ||||||
Function / homology | ![]() corticospinal neuron axon guidance / positive regulation of voltage-gated sodium channel activity / response to pyrethroid / detection of mechanical stimulus involved in sensory perception / voltage-gated sodium channel activity involved in Purkinje myocyte action potential / voltage-gated sodium channel activity involved in cardiac muscle cell action potential / regulation of sodium ion transmembrane transporter activity / voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization / membrane depolarization during Purkinje myocyte cell action potential / regulation of atrial cardiac muscle cell membrane depolarization ...corticospinal neuron axon guidance / positive regulation of voltage-gated sodium channel activity / response to pyrethroid / detection of mechanical stimulus involved in sensory perception / voltage-gated sodium channel activity involved in Purkinje myocyte action potential / voltage-gated sodium channel activity involved in cardiac muscle cell action potential / regulation of sodium ion transmembrane transporter activity / voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization / membrane depolarization during Purkinje myocyte cell action potential / regulation of atrial cardiac muscle cell membrane depolarization / cardiac conduction / membrane depolarization during cardiac muscle cell action potential / positive regulation of sodium ion transport / node of Ranvier / cardiac muscle cell action potential involved in contraction / regulation of ventricular cardiac muscle cell membrane repolarization / voltage-gated sodium channel complex / sodium channel inhibitor activity / locomotion / neuronal action potential propagation / Interaction between L1 and Ankyrins / voltage-gated sodium channel activity / sodium ion transport / Phase 0 - rapid depolarisation / behavioral response to pain / regulation of heart rate by cardiac conduction / detection of temperature stimulus involved in sensory perception of pain / membrane depolarization / intercalated disc / sodium ion transmembrane transport / sodium channel regulator activity / cardiac muscle contraction / sensory perception of pain / T-tubule / post-embryonic development / axon guidance / circadian rhythm / response to toxic substance / Sensory perception of sweet, bitter, and umami (glutamate) taste / positive regulation of neuron projection development / nervous system development / gene expression / response to heat / chemical synaptic transmission / perikaryon / transmembrane transporter binding / cell adhesion / inflammatory response / axon / synapse / extracellular region / plasma membrane Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å | ||||||
![]() | Fan, X. / Huang, J. / Yan, N. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Structural mapping of Na1.7 antagonists. Authors: Qiurong Wu / Jian Huang / Xiao Fan / Kan Wang / Xueqin Jin / Gaoxingyu Huang / Jiaao Li / Xiaojing Pan / Nieng Yan / ![]() ![]() Abstract: Voltage-gated sodium (Na) channels are targeted by a number of widely used and investigational drugs for the treatment of epilepsy, arrhythmia, pain, and other disorders. Despite recent advances in ...Voltage-gated sodium (Na) channels are targeted by a number of widely used and investigational drugs for the treatment of epilepsy, arrhythmia, pain, and other disorders. Despite recent advances in structural elucidation of Na channels, the binding mode of most Na-targeting drugs remains unknown. Here we report high-resolution cryo-EM structures of human Na1.7 treated with drugs and lead compounds with representative chemical backbones at resolutions of 2.6-3.2 Å. A binding site beneath the intracellular gate (site BIG) accommodates carbamazepine, bupivacaine, and lacosamide. Unexpectedly, a second molecule of lacosamide plugs into the selectivity filter from the central cavity. Fenestrations are popular sites for various state-dependent drugs. We show that vinpocetine, a synthetic derivative of a vinca alkaloid, and hardwickiic acid, a natural product with antinociceptive effect, bind to the III-IV fenestration, while vixotrigine, an analgesic candidate, penetrates the IV-I fenestration of the pore domain. Our results permit building a 3D structural map for known drug-binding sites on Na channels summarized from the present and previous structures. | ||||||
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 366.9 KB | Display | ![]() |
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PDB format | ![]() | 284.1 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 2.2 MB | Display | ![]() |
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Full document | ![]() | 2.2 MB | Display | |
Data in XML | ![]() | 63.3 KB | Display | |
Data in CIF | ![]() | 92.6 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 40239MC ![]() 8i5bC ![]() 8i5gC ![]() 8i5xC ![]() 8i5yC ![]() 8j4fC ![]() 8s9bC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Protein , 1 types, 1 molecules A
#1: Protein | Mass: 226620.047 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: Carbamazepine / Source: (gene. exp.) ![]() ![]() |
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-Sodium channel subunit beta- ... , 2 types, 2 molecules BC
#2: Protein | Mass: 24732.115 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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#3: Protein | Mass: 24355.859 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
-Sugars , 2 types, 8 molecules ![](data/chem/img/NAG.gif)
#4: Polysaccharide | Source method: isolated from a genetically manipulated source #5: Sugar | ChemComp-NAG / |
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-Non-polymers , 6 types, 42 molecules ![](data/chem/img/N6W.gif)
![](data/chem/img/P5S.gif)
![](data/chem/img/Y01.gif)
![](data/chem/img/LPE.gif)
![](data/chem/img/PCW.gif)
![](data/chem/img/HOH.gif)
![](data/chem/img/P5S.gif)
![](data/chem/img/Y01.gif)
![](data/chem/img/LPE.gif)
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#6: Chemical | ChemComp-N6W / | ||||||||
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#7: Chemical | #8: Chemical | ChemComp-Y01 / #9: Chemical | ChemComp-LPE / #10: Chemical | ChemComp-PCW / #11: Water | ChemComp-HOH / | |
-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 |
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Sample preparation
Component | Name: Human voltage-gated sodium channel Nav1.7 with beta subunits Type: COMPLEX / Entity ID: #1-#3 / Source: RECOMBINANT |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 1400 nm / Nominal defocus min: 1200 nm |
Image recording | Electron dose: 50 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.20_4459: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 287917 / Symmetry type: POINT | ||||||||||||||||||||||||
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