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- PDB-7sac: S-(+)-ketamine bound GluN1a-GluN2B NMDA receptors at 3.69 Angstro... -
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Open data
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Basic information
Entry | Database: PDB / ID: 7sac | |||||||||
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Title | S-(+)-ketamine bound GluN1a-GluN2B NMDA receptors at 3.69 Angstrom resolution | |||||||||
![]() | (Glutamate receptor ionotropic, NMDA ...) x 2 | |||||||||
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Function / homology | ![]() neurotransmitter receptor activity involved in regulation of postsynaptic membrane potential / cellular response to curcumin / cellular response to corticosterone stimulus / cellular response to magnesium starvation / regulation of postsynaptic cytosolic calcium ion concentration / sensory organ development / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | ![]() ![]() ![]() | |||||||||
![]() | Chou, T.-H. / Furukawa, H. | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural insights into binding of therapeutic channel blockers in NMDA receptors. Authors: Tsung-Han Chou / Max Epstein / Kevin Michalski / Eve Fine / Philip C Biggin / Hiro Furukawa / ![]() ![]() Abstract: Excitatory signaling mediated by N-methyl-D-aspartate receptor (NMDAR) is critical for brain development and function, as well as for neurological diseases and disorders. Channel blockers of NMDARs ...Excitatory signaling mediated by N-methyl-D-aspartate receptor (NMDAR) is critical for brain development and function, as well as for neurological diseases and disorders. Channel blockers of NMDARs are of medical interest owing to their potential for treating depression, Alzheimer's disease, and epilepsy. However, precise mechanisms underlying binding and channel blockade have remained limited owing to challenges in obtaining high-resolution structures at the binding site within the transmembrane domains. Here, we monitor the binding of three clinically important channel blockers: phencyclidine, ketamine, and memantine in GluN1-2B NMDARs at local resolutions of 2.5-3.5 Å around the binding site using single-particle electron cryo-microscopy, molecular dynamics simulations, and electrophysiology. The channel blockers form different extents of interactions with the pore-lining residues, which control mostly off-speeds but not on-speeds. Our comparative analyses of the three unique NMDAR channel blockers provide a blueprint for developing therapeutic compounds with minimal side effects. | |||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 539.9 KB | Display | ![]() |
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PDB format | ![]() | 433.5 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 24948MC ![]() 7saaC ![]() 7sabC ![]() 7sadC 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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1 |
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Components
-Glutamate receptor ionotropic, NMDA ... , 2 types, 4 molecules ACBD
#1: Protein | Mass: 95225.883 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() ![]() #2: Protein | Mass: 98888.945 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() ![]() |
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-Sugars , 2 types, 10 molecules ![](data/chem/img/NAG.gif)
#3: Polysaccharide | ![]() Source method: isolated from a genetically manipulated source #4: Sugar | ChemComp-NAG / ![]() |
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-Non-polymers , 3 types, 5 molecules ![](data/chem/img/GLY.gif)
![](data/chem/img/GLU.gif)
![](data/chem/img/JC9.gif)
![](data/chem/img/GLU.gif)
![](data/chem/img/JC9.gif)
#5: Chemical | ![]() #6: Chemical | ![]() #7: Chemical | ChemComp-JC9 / ( | ![]() |
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-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: ![]() |
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Sample preparation
Component | Name: Hetero-tetrameric GluN1a-GluN2B NMDA receptors / Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT |
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Source (natural) | Organism: ![]() ![]() ![]() |
Source (recombinant) | Organism: ![]() ![]() ![]() |
Buffer solution | pH: 7.5 |
Specimen | Conc.: 4 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied![]() ![]() |
Vitrification![]() | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 85 % / Chamber temperature: 285 K |
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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![]() |
Image recording | Electron dose: 57.6 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.19.1_4122: / Classification: refinement | ||||||||||||||||||||||||
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EM software | Name: cisTEM / Version: 1.0.2 / Category: 3D reconstruction![]() | ||||||||||||||||||||||||
CTF correction![]() | Type: NONE | ||||||||||||||||||||||||
3D reconstruction![]() | Resolution: 3.69 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 434625 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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