[English] 日本語
Yorodumi
- PDB-6usu: Crystal structure of GluN1/GluN2A ligand-binding domain in comple... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6usu
TitleCrystal structure of GluN1/GluN2A ligand-binding domain in complex with L689,560 and glutamate
Components
  • Glutamate receptor ionotropic, NMDA 1
  • Glutamate receptor ionotropic, NMDA 2A
KeywordsMETAL TRANSPORT / NMDARs / LBD / Ion channels
Function / homology
Function and homology information


neurotransmitter receptor transport, plasma membrane to endosome / regulation of response to alcohol / response to ammonium ion / receptor recycling / directional locomotion / response to environmental enrichment / pons maturation / positive regulation of Schwann cell migration / regulation of cell communication / EPHB-mediated forward signaling ...neurotransmitter receptor transport, plasma membrane to endosome / regulation of response to alcohol / response to ammonium ion / receptor recycling / directional locomotion / response to environmental enrichment / pons maturation / positive regulation of Schwann cell migration / regulation of cell communication / EPHB-mediated forward signaling / Assembly and cell surface presentation of NMDA receptors / serotonin metabolic process / olfactory learning / conditioned taste aversion / response to hydrogen sulfide / regulation of respiratory gaseous exchange / dendritic branch / positive regulation of inhibitory postsynaptic potential / cellular response to magnesium ion / protein localization to postsynaptic membrane / conditioned place preference / regulation of ARF protein signal transduction / response to methylmercury / response to other organism / propylene metabolic process / response to glycine / sleep / locomotion / dendritic spine organization / response to carbohydrate / cellular response to dsRNA / voltage-gated monoatomic cation channel activity / cellular response to lipid / regulation of monoatomic cation transmembrane transport / regulation of NMDA receptor activity / NMDA glutamate receptor activity / Synaptic adhesion-like molecules / RAF/MAP kinase cascade / NMDA selective glutamate receptor complex / response to manganese ion / parallel fiber to Purkinje cell synapse / response to morphine / cellular response to zinc ion / glutamate receptor signaling pathway / calcium ion transmembrane import into cytosol / glutamate binding / neuromuscular process / protein heterotetramerization / regulation of synapse assembly / positive regulation of reactive oxygen species biosynthetic process / male mating behavior / regulation of axonogenesis / regulation of dendrite morphogenesis / glycine binding / spinal cord development / positive regulation of calcium ion transport into cytosol / suckling behavior / response to amine / startle response / dopamine metabolic process / monoatomic cation transmembrane transport / response to lithium ion / modulation of excitatory postsynaptic potential / action potential / regulation of neuronal synaptic plasticity / associative learning / monoatomic cation transport / social behavior / ligand-gated monoatomic ion channel activity / positive regulation of excitatory postsynaptic potential / cellular response to glycine / excitatory synapse / positive regulation of dendritic spine maintenance / response to light stimulus / positive regulation of protein targeting to membrane / regulation of postsynaptic membrane potential / Unblocking of NMDA receptors, glutamate binding and activation / cellular response to manganese ion / postsynaptic density, intracellular component / phosphatase binding / glutamate receptor binding / neuron development / multicellular organismal response to stress / long-term memory / prepulse inhibition / calcium ion homeostasis / monoatomic cation channel activity / regulation of neuron apoptotic process / glutamate-gated receptor activity / synaptic cleft / response to fungicide / glutamate-gated calcium ion channel activity / presynaptic active zone membrane / cell adhesion molecule binding / sensory perception of pain / dendrite membrane / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / response to amphetamine / ionotropic glutamate receptor signaling pathway / hippocampal mossy fiber to CA3 synapse
Similarity search - Function
Glutamate [NMDA] receptor, epsilon subunit, C-terminal / N-methyl D-aspartate receptor 2B3 C-terminus / : / : / Ionotropic glutamate receptor, metazoa / Ligated ion channel L-glutamate- and glycine-binding site / Ionotropic glutamate receptor, L-glutamate and glycine-binding domain / Ligated ion channel L-glutamate- and glycine-binding site / Ligand-gated ion channel / : ...Glutamate [NMDA] receptor, epsilon subunit, C-terminal / N-methyl D-aspartate receptor 2B3 C-terminus / : / : / Ionotropic glutamate receptor, metazoa / Ligated ion channel L-glutamate- and glycine-binding site / Ionotropic glutamate receptor, L-glutamate and glycine-binding domain / Ligated ion channel L-glutamate- and glycine-binding site / Ligand-gated ion channel / : / Ionotropic glutamate receptor / Eukaryotic homologues of bacterial periplasmic substrate binding proteins. / Receptor, ligand binding region / Receptor family ligand binding region / Periplasmic binding protein-like I
Similarity search - Domain/homology
GLUTAMIC ACID / Chem-QGM / Glutamate receptor ionotropic, NMDA 1 / Glutamate receptor ionotropic, NMDA 2A
Similarity search - Component
Biological speciesRattus norvegicus (Norway rat)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.092 Å
AuthorsRomero-Hernandez, A. / Tajima, N. / Chou, T. / Furukawa, H.
Funding support United States, 2items
OrganizationGrant numberCountry
National Institutes of Health/National Human Genome Research Institute (NIH/NHGRI)NS111745 United States
National Institutes of Health/National Institute of Mental Health (NIH/NIMH)MH085926 United States
CitationJournal: Cell / Year: 2020
Title: Structural Basis of Functional Transitions in Mammalian NMDA Receptors.
Authors: Tsung-Han Chou / Nami Tajima / Annabel Romero-Hernandez / Hiro Furukawa /
Abstract: Excitatory neurotransmission meditated by glutamate receptors including N-methyl-D-aspartate receptors (NMDARs) is pivotal to brain development and function. NMDARs are heterotetramers composed of ...Excitatory neurotransmission meditated by glutamate receptors including N-methyl-D-aspartate receptors (NMDARs) is pivotal to brain development and function. NMDARs are heterotetramers composed of GluN1 and GluN2 subunits, which bind glycine and glutamate, respectively, to activate their ion channels. Despite importance in brain physiology, the precise mechanisms by which activation and inhibition occur via subunit-specific binding of agonists and antagonists remain largely unknown. Here, we show the detailed patterns of conformational changes and inter-subunit and -domain reorientation leading to agonist-gating and subunit-dependent competitive inhibition by providing multiple structures in distinct ligand states at 4 Å or better. The structures reveal that activation and competitive inhibition by both GluN1 and GluN2 antagonists occur by controlling the tension of the linker between the ligand-binding domain and the transmembrane ion channel of the GluN2 subunit. Our results provide detailed mechanistic insights into NMDAR pharmacology, activation, and inhibition, which are fundamental to the brain physiology.
History
DepositionOct 28, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 15, 2020Provider: repository / Type: Initial release
Revision 1.1Aug 5, 2020Group: Database references / Category: citation / Item: _citation.journal_volume / _citation.page_first
Revision 1.2Oct 11, 2023Group: Advisory / Data collection ...Advisory / Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / pdbx_unobs_or_zero_occ_atoms
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession
Revision 1.3Oct 23, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature / Item: _pdbx_entry_details.has_protein_modification

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Glutamate receptor ionotropic, NMDA 1
B: Glutamate receptor ionotropic, NMDA 2A
hetero molecules


Theoretical massNumber of molelcules
Total (without water)65,6534
Polymers65,1252
Non-polymers5272
Water4,486249
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2360 Å2
ΔGint-4 kcal/mol
Surface area25240 Å2
MethodPISA
Unit cell
Length a, b, c (Å)54.040, 87.341, 136.987
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein Glutamate receptor ionotropic, NMDA 1 / GluN1 / Glutamate [NMDA] receptor subunit zeta-1 / N-methyl-D-aspartate receptor subunit NR1 / NMD-R1


Mass: 33340.031 Da / Num. of mol.: 1 / Fragment: UNP residues 415-565, 684-821
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Grin1, Nmdar1 / Production host: Escherichia coli K-12 (bacteria) / References: UniProt: P35439
#2: Protein Glutamate receptor ionotropic, NMDA 2A / GluN2A / Glutamate [NMDA] receptor subunit epsilon-1 / N-methyl D-aspartate receptor subtype 2A / NR2A


Mass: 31785.299 Da / Num. of mol.: 1 / Fragment: UNP residues 402-539, 661-802
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Grin2a / Production host: Escherichia coli K-12 (bacteria) / References: UniProt: Q00959
#3: Chemical ChemComp-QGM / (2R,4S)-5,7-dichloro-4-[(phenylcarbamoyl)amino]-1,2,3,4-tetrahydroquinoline-2-carboxylic acid


Mass: 380.225 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C17H15Cl2N3O3 / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical ChemComp-GLU / GLUTAMIC ACID


Type: L-peptide linking / Mass: 147.129 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C5H9NO4 / Feature type: SUBJECT OF INVESTIGATION
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 249 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 2.48 Å3/Da / Density % sol: 50.44 %
Crystal growTemperature: 291 K / Method: evaporation / pH: 7
Details: 0.2 M HEPES, pH 7.0, 60-90 mM sodium chloride, 15-20% PEG2000 MME

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 23-ID-B / Wavelength: 1.1 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Apr 6, 2013
RadiationMonochromator: Double crystal cryo-cooled Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.1 Å / Relative weight: 1
ReflectionResolution: 2.09→40 Å / Num. obs: 38873 / % possible obs: 99.9 % / Redundancy: 7.6 % / Biso Wilson estimate: 25.56 Å2 / Rmerge(I) obs: 0.117 / Net I/σ(I): 17.1
Reflection shellResolution: 2.09→2.18 Å / Redundancy: 6 % / Rmerge(I) obs: 0.62 / Num. unique obs: 3781 / CC1/2: 0.814 / % possible all: 99.8

-
Processing

Software
NameVersionClassification
HKL-2000data scaling
PHENIX1.13_2998refinement
PDB_EXTRACT3.25data extraction
HKL-2000data reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB entry 4NF8

4nf8


Resolution: 2.092→38.161 Å / SU ML: 0.23 / Cross valid method: THROUGHOUT / σ(F): 1.36 / Phase error: 21.77
RfactorNum. reflection% reflection
Rfree0.2221 1881 4.87 %
Rwork0.1894 --
obs0.191 38642 98.83 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso max: 77.3 Å2 / Biso mean: 27.2215 Å2 / Biso min: 12.93 Å2
Refinement stepCycle: final / Resolution: 2.092→38.161 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4337 0 35 249 4621
Biso mean--22.63 29.27 -
Num. residues----552
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection Rwork% reflection obs (%)
2.092-2.14850.28361150.223241786
2.1485-2.21170.26611570.218275899
2.2117-2.2830.27191310.20482855100
2.283-2.36460.25611650.20632798100
2.3646-2.45930.26271530.20452827100
2.4593-2.57120.25991520.20992834100
2.5712-2.70670.23581490.20162829100
2.7067-2.87630.23851380.2032823100
2.8763-3.09820.23491260.20962874100
3.0982-3.40990.22371340.2022889100
3.4099-3.90280.1941580.17262874100
3.9028-4.91550.18911430.14842940100
4.9155-38.1610.18951600.18473043100

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more