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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 | |||||||||
![]() | TRANSPORT PROTEIN / Ligand-gated ion channel / ionotropic glutamate receptor / synaptic protein / voltage-gate ion channel | |||||||||
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 / sensitization / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration ...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 / sensitization / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration / EPHB-mediated forward signaling / neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration / response to hydrogen sulfide / Assembly and cell surface presentation of NMDA receptors / olfactory learning / regulation of protein kinase A signaling / conditioned taste aversion / dendritic branch / response to other organism / regulation of respiratory gaseous exchange / protein localization to postsynaptic membrane / positive regulation of inhibitory postsynaptic potential / apical dendrite / propylene metabolic process / response to glycine / regulation of ARF protein signal transduction / fear response / response to methylmercury / positive regulation of cysteine-type endopeptidase activity / voltage-gated monoatomic cation channel activity / cellular response to dsRNA / response to carbohydrate / negative regulation of dendritic spine maintenance / regulation of monoatomic cation transmembrane transport / interleukin-1 receptor binding / cellular response to lipid / response to morphine / NMDA glutamate receptor activity / positive regulation of glutamate secretion / response to growth hormone / Synaptic adhesion-like molecules / NMDA selective glutamate receptor complex / RAF/MAP kinase cascade / parallel fiber to Purkinje cell synapse / NMDA selective glutamate receptor signaling pathway / response to manganese ion / calcium ion transmembrane import into cytosol / glutamate binding / neuromuscular process / positive regulation of reactive oxygen species biosynthetic process / protein heterotetramerization / regulation of synapse assembly / glycine binding / positive regulation of calcium ion transport into cytosol / regulation of dendrite morphogenesis / regulation of axonogenesis / male mating behavior / heterocyclic compound binding / action potential / suckling behavior / behavioral response to pain / startle response / response to amine / receptor clustering / monoatomic cation transmembrane transport / regulation of neuronal synaptic plasticity / monoatomic cation transport / associative learning / positive regulation of excitatory postsynaptic potential / regulation of MAPK cascade / social behavior / response to magnesium ion / ligand-gated monoatomic ion channel activity / cellular response to organic cyclic compound / excitatory synapse / extracellularly glutamate-gated ion channel activity / cellular response to glycine / positive regulation of dendritic spine maintenance / small molecule binding / neuron development / behavioral fear response / regulation of postsynaptic membrane potential / Unblocking of NMDA receptors, glutamate binding and activation / postsynaptic density, intracellular component / phosphatase binding / cellular response to manganese ion / glutamate-gated calcium ion channel activity / calcium ion homeostasis / glutamate receptor binding / D2 dopamine receptor binding / multicellular organismal response to stress / prepulse inhibition / monoatomic cation channel activity / long-term memory / detection of mechanical stimulus involved in sensory perception of pain / regulation of neuron apoptotic process / response to electrical stimulus / synaptic cleft / response to mechanical stimulus / glutamate-gated receptor activity Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.69 Å | |||||||||
![]() | 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
Summary document | ![]() | 1.3 MB | Display | ![]() |
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Full document | ![]() | 1.4 MB | Display | |
Data in XML | ![]() | 86.1 KB | Display | |
Data in CIF | ![]() | 129 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-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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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: 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: 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: NO / Vitrification applied: YES |
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 | ||||||||||||||||||||||||
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