[English] 日本語
Yorodumi
- PDB-5tp9: Structure of the human GluN1/GluN2A LBD in complex with compound ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5tp9
TitleStructure of the human GluN1/GluN2A LBD in complex with compound 2 (GNE9178)
Components(Glutamate receptor ionotropic, NMDA ...) x 2
KeywordsTRANSPORT PROTEIN / NMDA receptor / glutamate / glycine / calcium channel / membrane
Function / homology
Function and homology information


excitatory chemical synaptic transmission / directional locomotion / Synaptic adhesion-like molecules / serotonin metabolic process / activation of cysteine-type endopeptidase activity / protein localization to postsynaptic membrane / propylene metabolic process / response to glycine / sleep / regulation of monoatomic cation transmembrane transport ...excitatory chemical synaptic transmission / directional locomotion / Synaptic adhesion-like molecules / serotonin metabolic process / activation of cysteine-type endopeptidase activity / protein localization to postsynaptic membrane / propylene metabolic process / response to glycine / sleep / regulation of monoatomic cation transmembrane transport / Assembly and cell surface presentation of NMDA receptors / NMDA glutamate receptor activity / Neurexins and neuroligins / NMDA selective glutamate receptor complex / calcium ion transmembrane import into cytosol / glutamate binding / glutamate receptor signaling pathway / protein heterotetramerization / positive regulation of calcium ion transport into cytosol / positive regulation of reactive oxygen species biosynthetic process / glycine binding / startle response / Negative regulation of NMDA receptor-mediated neuronal transmission / Unblocking of NMDA receptors, glutamate binding and activation / dopamine metabolic process / monoatomic cation transmembrane transport / regulation of neuronal synaptic plasticity / monoatomic cation transport / Long-term potentiation / excitatory synapse / ligand-gated monoatomic ion channel activity / positive regulation of excitatory postsynaptic potential / calcium ion homeostasis / synaptic cleft / MECP2 regulates neuronal receptors and channels / glutamate-gated calcium ion channel activity / EPHB-mediated forward signaling / sensory perception of pain / response to amphetamine / Ras activation upon Ca2+ influx through NMDA receptor / ionotropic glutamate receptor signaling pathway / neurogenesis / positive regulation of synaptic transmission, glutamatergic / regulation of membrane potential / excitatory postsynaptic potential / synaptic transmission, glutamatergic / synaptic membrane / long-term synaptic potentiation / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / postsynaptic density membrane / brain development / visual learning / cytoplasmic vesicle membrane / protein catabolic process / regulation of synaptic plasticity / negative regulation of protein catabolic process / terminal bouton / memory / response to wounding / synaptic vesicle / signaling receptor activity / presynaptic membrane / amyloid-beta binding / RAF/MAP kinase cascade / chemical synaptic transmission / postsynaptic membrane / response to ethanol / dendritic spine / postsynaptic density / learning or memory / calmodulin binding / neuron projection / positive regulation of apoptotic process / response to xenobiotic stimulus / glutamatergic synapse / dendrite / calcium ion binding / synapse / endoplasmic reticulum membrane / protein-containing complex binding / cell surface / positive regulation of transcription by RNA polymerase II / zinc ion binding / plasma membrane / cytoplasm
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 II / Periplasmic binding protein-like I / D-Maltodextrin-Binding Protein; domain 2 / 3-Layer(aba) Sandwich / Alpha Beta
Similarity search - Domain/homology
Chem-7H0 / ACETATE ION / GLUTAMIC ACID / GLYCINE / Glutamate receptor ionotropic, NMDA 1 / Glutamate receptor ionotropic, NMDA 2A
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.4 Å
AuthorsWallweber, H.J.A. / Lupardus, P.J.
CitationJournal: ACS Med Chem Lett / Year: 2017
Title: GluN2A-Selective Pyridopyrimidinone Series of NMDAR Positive Allosteric Modulators with an Improved in Vivo Profile.
Authors: Villemure, E. / Volgraf, M. / Jiang, Y. / Wu, G. / Ly, C.Q. / Yuen, P.W. / Lu, A. / Luo, X. / Liu, M. / Zhang, S. / Lupardus, P.J. / Wallweber, H.J. / Liederer, B.M. / Deshmukh, G. / Plise, ...Authors: Villemure, E. / Volgraf, M. / Jiang, Y. / Wu, G. / Ly, C.Q. / Yuen, P.W. / Lu, A. / Luo, X. / Liu, M. / Zhang, S. / Lupardus, P.J. / Wallweber, H.J. / Liederer, B.M. / Deshmukh, G. / Plise, E. / Tay, S. / Wang, T.M. / Hanson, J.E. / Hackos, D.H. / Scearce-Levie, K. / Schwarz, J.B. / Sellers, B.D.
History
DepositionOct 20, 2016Deposition site: RCSB / Processing site: RCSB
Revision 1.0Nov 30, 2016Provider: repository / Type: Initial release
Revision 1.1Dec 28, 2016Group: Database references
Revision 1.2Feb 8, 2017Group: Database references
Revision 1.3Oct 16, 2024Group: Data collection / Database references / Structure summary
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_entry_details / pdbx_modification_feature
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

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


Theoretical massNumber of molelcules
Total (without water)66,0347
Polymers65,2932
Non-polymers7415
Water2,234124
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2450 Å2
ΔGint-11 kcal/mol
Surface area25180 Å2
MethodPISA
Unit cell
Length a, b, c (Å)56.260, 89.780, 120.860
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

-
Components

-
Glutamate receptor ionotropic, NMDA ... , 2 types, 2 molecules AB

#1: Protein Glutamate receptor ionotropic, NMDA 2A / GluN2A / Glutamate [NMDA] receptor subunit epsilon-1 / N-methyl D-aspartate receptor subtype 2A / hNR2A


Mass: 31883.441 Da / Num. of mol.: 1
Fragment: Ligand binding domain (UNP residues 401-539, GT linker, UNP residues 661-802)
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GRIN2A, NMDAR2A / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q12879
#2: Protein Glutamate receptor ionotropic, NMDA 1 / GluN1 / Glutamate [NMDA] receptor subunit zeta-1 / N-methyl-D-aspartate receptor subunit NR1 / NMD-R1


Mass: 33409.074 Da / Num. of mol.: 1
Fragment: UNP residues 394-544, GT linker, UNP residues 663-800
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GRIN1, NMDAR1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q05586

-
Non-polymers , 6 types, 129 molecules

#3: Chemical ChemComp-ACT / ACETATE ION


Mass: 59.044 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Formula: C2H3O2
#4: Chemical ChemComp-GLU / GLUTAMIC ACID


Type: L-peptide linking / Mass: 147.129 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C5H9NO4
#5: Chemical ChemComp-7H0 / 7-{[5-chloro-3-(trifluoromethyl)-1H-pyrazol-1-yl]methyl}-N-ethyl-2-methyl-5-oxo-5H-[1,3]thiazolo[3,2-a]pyrimidine-3-carboxamide


Mass: 419.809 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C15H13ClF3N5O2S
#6: Chemical ChemComp-CA / CALCIUM ION


Mass: 40.078 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Formula: Ca
#7: Chemical ChemComp-GLY / GLYCINE


Type: peptide linking / Mass: 75.067 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C2H5NO2
#8: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 124 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.34 Å3/Da / Density % sol: 47.38 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop / pH: 7
Details: 0.1 M HEPES, pH 7.0, 10-13% PEG8000, 2 mM calcium acetate

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.2 / Wavelength: 1 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Jan 15, 2014
RadiationMonochromator: liquid nitrogen-cooled dual crystal Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.4→50 Å / Num. obs: 24941 / % possible obs: 100 % / Redundancy: 5.9 % / Biso Wilson estimate: 55.22 Å2 / Rmerge(I) obs: 0.081 / Net I/σ(I): 19.1
Reflection shellResolution: 2.4→2.49 Å / Redundancy: 6.1 % / Rmerge(I) obs: 0.722 / Mean I/σ(I) obs: 2.7 / % possible all: 100

-
Processing

Software
NameVersionClassification
BUSTER2.11.6refinement
HKL-2000data reduction
SCALEPACKdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.4→47.67 Å / Cor.coef. Fo:Fc: 0.948 / Cor.coef. Fo:Fc free: 0.93 / Rfactor Rfree error: 0 / SU R Cruickshank DPI: 0.377 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.392 / SU Rfree Blow DPI: 0.241 / SU Rfree Cruickshank DPI: 0.242
RfactorNum. reflection% reflectionSelection details
Rfree0.237 1251 5.03 %RANDOM
Rwork0.19 ---
obs0.192 24871 99.7 %-
Displacement parametersBiso mean: 53.11 Å2
Baniso -1Baniso -2Baniso -3
1--2.6684 Å20 Å20 Å2
2--4.0542 Å20 Å2
3----1.3858 Å2
Refine analyzeLuzzati coordinate error obs: 0.29 Å
Refinement stepCycle: 1 / Resolution: 2.4→47.67 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4382 0 32 124 4538
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.014546HARMONIC2
X-RAY DIFFRACTIONt_angle_deg1.086161HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d1579SINUSOIDAL2
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes107HARMONIC2
X-RAY DIFFRACTIONt_gen_planes686HARMONIC5
X-RAY DIFFRACTIONt_it4546HARMONIC20
X-RAY DIFFRACTIONt_nbd0SEMIHARMONIC5
X-RAY DIFFRACTIONt_omega_torsion3.11
X-RAY DIFFRACTIONt_other_torsion18.28
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_chiral_improper_torsion596SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact5142SEMIHARMONIC4
LS refinement shellResolution: 2.39→2.5 Å / Rfactor Rfree error: 0 / Total num. of bins used: 12
RfactorNum. reflection% reflection
Rfree0.326 120 4.12 %
Rwork0.228 2794 -
all0.232 2914 -
obs--97.81 %

+
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