[English] 日本語
Yorodumi
- PDB-2xxh: Crystal structure of 1-(4-(2-oxo-2-(1-pyrrolidinyl)ethyl)phenyl)-... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 2xxh
TitleCrystal structure of 1-(4-(2-oxo-2-(1-pyrrolidinyl)ethyl)phenyl)-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazole in complex with the ligand binding domain of the Rat GluA2 receptor and glutamate at 1.5A resolution.
ComponentsGLUTAMATE RECEPTOR 2
KeywordsTRANSPORT PROTEIN / AMPA RECEPTOR LIGAND-BINDING CORE / ION CHANNEL
Function / homology
Function and homology information


regulation of synaptic plasticity by chemical substance / spine synapse / dendritic spine neck / dendritic spine cytoplasm / cellular response to amine stimulus / response to phorbol 13-acetate 12-myristate / dendritic spine head / Activation of AMPA receptors / ligand-gated monoatomic cation channel activity / perisynaptic space ...regulation of synaptic plasticity by chemical substance / spine synapse / dendritic spine neck / dendritic spine cytoplasm / cellular response to amine stimulus / response to phorbol 13-acetate 12-myristate / dendritic spine head / Activation of AMPA receptors / ligand-gated monoatomic cation channel activity / perisynaptic space / response to lithium ion / Trafficking of GluR2-containing AMPA receptors / AMPA glutamate receptor activity / AMPA glutamate receptor clustering / regulation of receptor recycling / kainate selective glutamate receptor activity / AMPA glutamate receptor complex / extracellularly glutamate-gated ion channel activity / ionotropic glutamate receptor complex / cellular response to glycine / immunoglobulin binding / asymmetric synapse / Unblocking of NMDA receptors, glutamate binding and activation / response to fungicide / glutamate receptor binding / positive regulation of synaptic transmission / conditioned place preference / regulation of synaptic transmission, glutamatergic / cytoskeletal protein binding / extracellular ligand-gated monoatomic ion channel activity / glutamate-gated receptor activity / cellular response to brain-derived neurotrophic factor stimulus / regulation of long-term synaptic depression / glutamate-gated calcium ion channel activity / somatodendritic compartment / presynaptic active zone membrane / ionotropic glutamate receptor binding / ionotropic glutamate receptor signaling pathway / excitatory synapse / dendrite cytoplasm / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / dendrite membrane / positive regulation of excitatory postsynaptic potential / SNARE binding / synaptic membrane / establishment of protein localization / synaptic transmission, glutamatergic / PDZ domain binding / cerebral cortex development / dendritic shaft / protein tetramerization / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / long-term synaptic potentiation / receptor internalization / postsynaptic density membrane / Schaffer collateral - CA1 synapse / modulation of chemical synaptic transmission / terminal bouton / synaptic vesicle membrane / synaptic vesicle / signaling receptor activity / amyloid-beta binding / presynapse / growth cone / chemical synaptic transmission / scaffold protein binding / presynaptic membrane / dendritic spine / perikaryon / neuron projection / postsynaptic membrane / postsynaptic density / external side of plasma membrane / axon / neuronal cell body / dendrite / protein kinase binding / synapse / glutamatergic synapse / protein-containing complex binding / perinuclear region of cytoplasm / cell surface / endoplasmic reticulum / protein-containing complex / membrane / identical protein binding / plasma membrane
Similarity search - Function
Ionotropic glutamate receptor, metazoa / Ligated ion channel L-glutamate- and glycine-binding site / Ligand-gated ion channel / Ionotropic glutamate receptor, L-glutamate and glycine-binding domain / Ligated ion channel L-glutamate- and glycine-binding site / : / Ionotropic glutamate receptor / Eukaryotic homologues of bacterial periplasmic substrate binding proteins. / Periplasmic binding protein-like II / Receptor, ligand binding region ...Ionotropic glutamate receptor, metazoa / Ligated ion channel L-glutamate- and glycine-binding site / Ligand-gated ion channel / Ionotropic glutamate receptor, L-glutamate and glycine-binding domain / Ligated ion channel L-glutamate- and glycine-binding site / : / Ionotropic glutamate receptor / Eukaryotic homologues of bacterial periplasmic substrate binding proteins. / Periplasmic binding protein-like II / Receptor, ligand binding region / Receptor family ligand binding region / D-Maltodextrin-Binding Protein; domain 2 / Periplasmic binding protein-like I / 3-Layer(aba) Sandwich / Alpha Beta
Similarity search - Domain/homology
Chem-1NG / GLUTAMIC ACID / Glutamate receptor 2
Similarity search - Component
Biological speciesRATTUS NORVEGICUS (Norway rat)
MethodX-RAY DIFFRACTION / SYNCHROTRON / OTHER / Resolution: 1.5 Å
AuthorsWard, S.E. / Harries, M. / Aldegheri, L. / Austin, N.E. / Ballantine, S. / Ballini, E. / Bradley, D.M. / Bax, B.D. / Clarke, B.P. / Harris, A.J. ...Ward, S.E. / Harries, M. / Aldegheri, L. / Austin, N.E. / Ballantine, S. / Ballini, E. / Bradley, D.M. / Bax, B.D. / Clarke, B.P. / Harris, A.J. / Harrison, S.A. / Melarange, R.A. / Mookherjee, C. / Mosley, J. / DalNegro, G. / Oliosi, B. / Smith, K.J. / Thewlis, K.M. / Woollard, P.M. / Yusaf, S.P.
CitationJournal: J.Med.Chem. / Year: 2011
Title: Integration of Lead Optimization with Crystallography for a Membrane-Bound Ion Channel Target: Discovery of a New Class of Ampa Receptor Positive Allosteric Modulators.
Authors: Ward, S.E. / Harries, M. / Aldegheri, L. / Austin, N.E. / Ballantine, S. / Ballini, E. / Bradley, D.M. / Bax, B.D. / Clarke, B.P. / Harris, A.J. / Harrison, S.A. / Melarange, R.A. / ...Authors: Ward, S.E. / Harries, M. / Aldegheri, L. / Austin, N.E. / Ballantine, S. / Ballini, E. / Bradley, D.M. / Bax, B.D. / Clarke, B.P. / Harris, A.J. / Harrison, S.A. / Melarange, R.A. / Mookherjee, C. / Mosley, J. / Dal Negro, G. / Oliosi, B. / Smith, K.J. / Thewlis, K.M. / Woollard, P.M. / Yusaf, S.P.
History
DepositionNov 10, 2010Deposition site: PDBE / Processing site: PDBE
Revision 1.0Apr 6, 2011Provider: repository / Type: Initial release
Revision 1.1Sep 28, 2011Group: Database references / Version format compliance
Revision 1.2Nov 20, 2024Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Other / Structure summary
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_database_status / pdbx_entry_details / pdbx_modification_feature / pdbx_struct_conn_angle / struct_conn / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_database_status.status_code_sf / _pdbx_entry_details.has_protein_modification / _pdbx_struct_conn_angle.ptnr1_auth_asym_id / _pdbx_struct_conn_angle.ptnr1_auth_comp_id / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr1_label_asym_id / _pdbx_struct_conn_angle.ptnr1_label_atom_id / _pdbx_struct_conn_angle.ptnr1_label_comp_id / _pdbx_struct_conn_angle.ptnr1_label_seq_id / _pdbx_struct_conn_angle.ptnr1_symmetry / _pdbx_struct_conn_angle.ptnr2_auth_asym_id / _pdbx_struct_conn_angle.ptnr2_auth_seq_id / _pdbx_struct_conn_angle.ptnr2_label_asym_id / _pdbx_struct_conn_angle.ptnr3_auth_asym_id / _pdbx_struct_conn_angle.ptnr3_auth_comp_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_label_asym_id / _pdbx_struct_conn_angle.ptnr3_label_atom_id / _pdbx_struct_conn_angle.ptnr3_label_comp_id / _pdbx_struct_conn_angle.ptnr3_label_seq_id / _pdbx_struct_conn_angle.ptnr3_symmetry / _pdbx_struct_conn_angle.value / _struct_conn.pdbx_dist_value / _struct_conn.ptnr1_auth_asym_id / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr1_symmetry / _struct_conn.ptnr2_auth_asym_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id / _struct_conn.ptnr2_label_seq_id / _struct_conn.ptnr2_symmetry / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: GLUTAMATE RECEPTOR 2
B: GLUTAMATE RECEPTOR 2
C: GLUTAMATE RECEPTOR 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)89,20314
Polymers87,5843
Non-polymers1,61911
Water9,386521
1
B: GLUTAMATE RECEPTOR 2
hetero molecules

B: GLUTAMATE RECEPTOR 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)60,02314
Polymers58,3892
Non-polymers1,63412
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation2_665-x+1,-y+1,z1
Buried area2770 Å2
ΔGint-125 kcal/mol
Surface area23220 Å2
MethodPISA
2
A: GLUTAMATE RECEPTOR 2
C: GLUTAMATE RECEPTOR 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)59,1927
Polymers58,3892
Non-polymers8025
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2210 Å2
ΔGint-41 kcal/mol
Surface area22670 Å2
MethodPISA
Unit cell
Length a, b, c (Å)114.374, 163.583, 47.481
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number18
Space group name H-MP21212

-
Components

-
Protein , 1 types, 3 molecules ABC

#1: Protein GLUTAMATE RECEPTOR 2 / GLUR-2 / AMPA-SELECTIVE GLUTAMATE RECEPTOR 2 / GLUR-B / GLUR-K2 / GLUTAMATE RECEPTOR IONOTROPIC\ / ...GLUR-2 / AMPA-SELECTIVE GLUTAMATE RECEPTOR 2 / GLUR-B / GLUR-K2 / GLUTAMATE RECEPTOR IONOTROPIC\ / AMPA 2 / GLUA2


Mass: 29194.658 Da / Num. of mol.: 3 / Fragment: LIGAND BINDING DOMAIN, RESIDUES 413-527,653-796 / Mutation: YES
Source method: isolated from a genetically manipulated source
Details: GLUA2FLOPS1-GLYTHR-S2 / Source: (gene. exp.) RATTUS NORVEGICUS (Norway rat) / Production host: ESCHERICHIA COLI (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: P19491

-
Non-polymers , 5 types, 532 molecules

#2: Chemical ChemComp-GLU / GLUTAMIC ACID


Type: L-peptide linking / Mass: 147.129 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C5H9NO4
#3: Chemical ChemComp-1NG / 1-{4-[2-OXO-2-(1-PYRROLIDINYL)ETHYL]PHENYL}-3-( TRIFLUOROMETHYL)-4,5,6,7-TETRAHYDRO-1H-INDAZOLE


Mass: 377.403 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C20H22F3N3O
#4: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: SO4
#5: Chemical
ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 5 / Source method: obtained synthetically / Formula: Zn
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 521 / Source method: isolated from a natural source / Formula: H2O

-
Details

Compound detailsENGINEERED RESIDUE IN CHAIN A, ASN 775 TO SER ENGINEERED RESIDUE IN CHAIN B, ASN 775 TO SER ...ENGINEERED RESIDUE IN CHAIN A, ASN 775 TO SER ENGINEERED RESIDUE IN CHAIN B, ASN 775 TO SER ENGINEERED RESIDUE IN CHAIN C, ASN 775 TO SER
Has protein modificationY

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION

-
Sample preparation

CrystalDensity Matthews: 2.54 Å3/Da / Density % sol: 51.49 % / Description: NONE

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Type: ESRF / Wavelength: 0.93928
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.93928 Å / Relative weight: 1
ReflectionResolution: 1.5→30 Å / Num. obs: 134500 / % possible obs: 94.8 % / Observed criterion σ(I): 0 / Redundancy: 2.8 % / Biso Wilson estimate: 18.02 Å2 / Rmerge(I) obs: 0.07 / Net I/σ(I): 11.4
Reflection shellResolution: 1.5→1.58 Å / Redundancy: 2.5 % / Rmerge(I) obs: 0.39 / Mean I/σ(I) obs: 2.6 / % possible all: 96.5

-
Processing

SoftwareName: REFMAC / Version: 5.5.0109 / Classification: refinement
RefinementMethod to determine structure: OTHER
Starting model: NONE

Resolution: 1.5→20 Å / Cor.coef. Fo:Fc: 0.955 / Cor.coef. Fo:Fc free: 0.945 / SU B: 1.308 / SU ML: 0.049 / Cross valid method: THROUGHOUT / ESU R: 0.079 / ESU R Free: 0.078 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS.
RfactorNum. reflection% reflectionSelection details
Rfree0.21757 6704 5 %RANDOM
Rwork0.19367 ---
obs0.19487 127261 93.5 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å
Displacement parametersBiso mean: 21.093 Å2
Baniso -1Baniso -2Baniso -3
1-0.27 Å20 Å20 Å2
2--0.23 Å20 Å2
3----0.5 Å2
Refinement stepCycle: LAST / Resolution: 1.5→20 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6005 0 94 521 6620
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0090.0226391
X-RAY DIFFRACTIONr_bond_other_d
X-RAY DIFFRACTIONr_angle_refined_deg1.3442.0058641
X-RAY DIFFRACTIONr_angle_other_deg
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.5015810
X-RAY DIFFRACTIONr_dihedral_angle_2_deg31.7324.403243
X-RAY DIFFRACTIONr_dihedral_angle_3_deg12.397151168
X-RAY DIFFRACTIONr_dihedral_angle_4_deg16.5291529
X-RAY DIFFRACTIONr_chiral_restr0.0840.2946
X-RAY DIFFRACTIONr_gen_planes_refined0.0110.0214708
X-RAY DIFFRACTIONr_gen_planes_other
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it1.11423964
X-RAY DIFFRACTIONr_mcbond_other
X-RAY DIFFRACTIONr_mcangle_it2.17356368
X-RAY DIFFRACTIONr_mcangle_other
X-RAY DIFFRACTIONr_scbond_it3.25362427
X-RAY DIFFRACTIONr_scbond_other
X-RAY DIFFRACTIONr_scangle_it4.99882273
X-RAY DIFFRACTIONr_scangle_other
X-RAY DIFFRACTIONr_long_range_B_refined
X-RAY DIFFRACTIONr_long_range_B_other
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 1.5→1.539 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.294 431 -
Rwork0.254 9198 -
obs--92.1 %

+
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