[English] 日本語
Yorodumi
- PDB-5ehc: Co-crystal structure of eIF4E with nucleotide mimetic inhibitor. -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5ehc
TitleCo-crystal structure of eIF4E with nucleotide mimetic inhibitor.
Components
  • Eukaryotic translation initiation factor 4 gamma 1
  • Eukaryotic translation initiation factor 4E
KeywordsTRANSLATION / Complex / inhibitor / eIF4E
Function / homology
Function and homology information


positive regulation of eukaryotic translation initiation factor 4F complex assembly / : / positive regulation of translation in response to endoplasmic reticulum stress / eukaryotic initiation factor 4G binding / cap-dependent translational initiation / Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S / eukaryotic initiation factor 4E binding / regulation of translation at postsynapse, modulating synaptic transmission / regulation of cellular response to stress / RNA cap binding ...positive regulation of eukaryotic translation initiation factor 4F complex assembly / : / positive regulation of translation in response to endoplasmic reticulum stress / eukaryotic initiation factor 4G binding / cap-dependent translational initiation / Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S / eukaryotic initiation factor 4E binding / regulation of translation at postsynapse, modulating synaptic transmission / regulation of cellular response to stress / RNA cap binding / eukaryotic translation initiation factor 4F complex / chromatoid body / Z-decay: degradation of maternal mRNAs by zygotically expressed factors / translation factor activity, RNA binding / mRNA cap binding / Deadenylation of mRNA / miRNA-mediated gene silencing by inhibition of translation / RNA 7-methylguanosine cap binding / Transport of the SLBP independent Mature mRNA / Transport of the SLBP Dependant Mature mRNA / M-decay: degradation of maternal mRNAs by maternally stored factors / Transport of Mature mRNA Derived from an Intronless Transcript / RISC complex / regulation of translational initiation / positive regulation of protein localization to cell periphery / Ribosomal scanning and start codon recognition / stem cell population maintenance / negative regulation of neuron differentiation / Translation initiation complex formation / positive regulation of protein metabolic process / mTORC1-mediated signalling / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / GTP hydrolysis and joining of the 60S ribosomal subunit / cellular response to dexamethasone stimulus / L13a-mediated translational silencing of Ceruloplasmin expression / positive regulation of G1/S transition of mitotic cell cycle / regulation of presynapse assembly / behavioral fear response / mRNA export from nucleus / cellular response to nutrient levels / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / energy homeostasis / translation initiation factor binding / translation initiation factor activity / positive regulation of neuron differentiation / positive regulation of mitotic cell cycle / negative regulation of autophagy / AUF1 (hnRNP D0) binds and destabilizes mRNA / translational initiation / P-body / G1/S transition of mitotic cell cycle / ISG15 antiviral mechanism / Regulation of expression of SLITs and ROBOs / cytoplasmic ribonucleoprotein granule / neuron differentiation / cytoplasmic stress granule / regulation of translation / positive regulation of cell growth / molecular adaptor activity / DNA-binding transcription factor binding / postsynapse / negative regulation of translation / nuclear speck / ribosome / translation / mRNA binding / perinuclear region of cytoplasm / glutamatergic synapse / enzyme binding / RNA binding / extracellular exosome / ATP binding / nucleus / membrane / cytoplasm / cytosol
Similarity search - Function
RNA Cap, Translation Initiation Factor Eif4e / RNA Cap, Translation Initiation Factor Eif4e / Eukaryotic translation initiation factor 4E (eIF-4E), conserved site / Eukaryotic initiation factor 4E signature. / Translation Initiation factor eIF- 4e / Eukaryotic initiation factor 4E / Translation Initiation factor eIF- 4e-like / eIF4-gamma/eIF5/eIF2-epsilon / Domain at the C-termini of GCD6, eIF-2B epsilon, eIF-4 gamma and eIF-5 / W2 domain ...RNA Cap, Translation Initiation Factor Eif4e / RNA Cap, Translation Initiation Factor Eif4e / Eukaryotic translation initiation factor 4E (eIF-4E), conserved site / Eukaryotic initiation factor 4E signature. / Translation Initiation factor eIF- 4e / Eukaryotic initiation factor 4E / Translation Initiation factor eIF- 4e-like / eIF4-gamma/eIF5/eIF2-epsilon / Domain at the C-termini of GCD6, eIF-2B epsilon, eIF-4 gamma and eIF-5 / W2 domain / W2 domain profile. / Initiation factor eIF-4 gamma, MA3 / MA3 domain / MI domain profile. / Domain in DAP-5, eIF4G, MA-3 and other proteins. / MIF4G domain / Middle domain of eukaryotic initiation factor 4G (eIF4G) / MIF4G-like, type 3 / Armadillo-type fold / 2-Layer Sandwich / Alpha Beta
Similarity search - Domain/homology
Chem-5NX / Eukaryotic translation initiation factor 4E / Eukaryotic translation initiation factor 4 gamma 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.4 Å
AuthorsNowicki, M.W. / Walkinshaw, M.D. / Fischer, P.M.
Funding support United Kingdom, 1items
OrganizationGrant numberCountry
United Kingdom
CitationJournal: Eur.J.Med.Chem. / Year: 2016
Title: Design of nucleotide-mimetic and non-nucleotide inhibitors of the translation initiation factor eIF4E: Synthesis, structural and functional characterisation.
Authors: Soukarieh, F. / Nowicki, M.W. / Bastide, A. / Poyry, T. / Jones, C. / Dudek, K. / Patwardhan, G. / Meullenet, F. / Oldham, N.J. / Walkinshaw, M.D. / Willis, A.E. / Fischer, P.M.
History
DepositionOct 28, 2015Deposition site: RCSB / Processing site: PDBE
Revision 1.0Sep 7, 2016Provider: repository / Type: Initial release
Revision 1.1Sep 14, 2016Group: Database references
Revision 1.2Jan 10, 2024Group: 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
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Eukaryotic translation initiation factor 4E
B: Eukaryotic translation initiation factor 4 gamma 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)27,4853
Polymers26,9812
Non-polymers5041
Water2,504139
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1340 Å2
ΔGint-6 kcal/mol
Surface area11010 Å2
MethodPISA
Unit cell
Length a, b, c (Å)38.489, 52.177, 125.698
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number18
Space group name H-MP21221

-
Components

#1: Protein Eukaryotic translation initiation factor 4E / eIF4E / eIF-4F 25 kDa subunit / mRNA cap-binding protein


Mass: 25130.242 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: EIF4E, EIF4EL1, EIF4F / Plasmid: pET11d / Production host: Escherichia coli BL21(DE3) (bacteria) / Variant (production host): Rosetta PLysS / References: UniProt: P06730
#2: Protein/peptide Eukaryotic translation initiation factor 4 gamma 1 / eIF-4G1 / p220


Mass: 1851.155 Da / Num. of mol.: 1 / Fragment: eIF4E binding sequence, UNP residues 634-647 / Source method: obtained synthetically / Details: commercial synthesis / Source: (synth.) Homo sapiens (human) / References: UniProt: Q04637
#3: Chemical ChemComp-5NX / 3-[[(2~{R},3~{S},4~{R},5~{R})-5-[2-azanyl-7-[(3-chlorophenyl)methyl]-6-oxidanylidene-1~{H}-purin-7-ium-9-yl]-3,4-bis(oxidanyl)oxolan-2-yl]methylamino]-4-oxidanyl-cyclobut-3-ene-1,2-dione


Mass: 503.873 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C21H20ClN6O7
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 139 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.34 Å3/Da / Density % sol: 47.41 %
Crystal growTemperature: 291 K / Method: vapor diffusion, hanging drop / pH: 7.5
Details: 21-31% PEG 8000, 1???3% (NH4)2SO4, 100 mM HEPES, pH 7.5, 1 round of seeding

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I04-1 / Wavelength: 0.9173 Å
DetectorType: DECTRIS PILATUS 300K / Detector: PIXEL / Date: Jul 8, 2011
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9173 Å / Relative weight: 1
ReflectionResolution: 2.4→62.849 Å / Num. all: 10425 / Num. obs: 10425 / % possible obs: 99.7 % / Redundancy: 6.4 % / Rpim(I) all: 0.082 / Rrim(I) all: 0.21 / Rsym value: 0.192 / Net I/av σ(I): 1.595 / Net I/σ(I): 8.9 / Num. measured all: 66558
Reflection shell

Diffraction-ID: 1 / Rejects: _

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. measured allNum. unique allRpim(I) allRsym valueNet I/σ(I) obs% possible all
2.4-2.536.70.3392.1975214660.140.3395.399.7
2.53-2.686.60.2752.6932514130.1150.2756.3100
2.68-2.876.10.2123.4796213030.0930.2127.398.9
2.87-3.16.60.164.5837912620.0660.168.7100
3.1-3.396.80.1345.4779311540.0550.1349.9100
3.39-3.796.10.4021653310640.1740.4027.5100
3.79-4.385.90.1523.854929320.0670.15210.799.5
4.38-5.376.60.0719.952748020.030.07113.199.8
5.37-7.596.10.0729.439166460.0310.07214.4100
7.59-28.3455.60.03121.121323830.0140.03117.597.4

-
Processing

Software
NameVersionClassification
SCALA3.3.16data scaling
PHENIXrefinement
PDB_EXTRACT3.15data extraction
XDSdata reduction
PHENIXphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 2w97

2w97


Resolution: 2.4→28.345 Å / SU ML: 0.31 / Cross valid method: NONE / σ(F): 1.35 / Phase error: 24.61 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2642 485 4.74 %
Rwork0.2183 9748 -
obs0.2205 10233 98.02 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 70.15 Å2 / Biso mean: 20.0172 Å2 / Biso min: 3.94 Å2
Refinement stepCycle: final / Resolution: 2.4→28.345 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1672 0 35 139 1846
Biso mean--42.42 21.58 -
Num. residues----200
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0091753
X-RAY DIFFRACTIONf_angle_d1.0272374
X-RAY DIFFRACTIONf_chiral_restr0.059244
X-RAY DIFFRACTIONf_plane_restr0.005299
X-RAY DIFFRACTIONf_dihedral_angle_d17.042647
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 3

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
2.4-2.7470.30391670.217732183385100
2.747-3.460.29071650.22213235340099
3.46-28.34690.22581530.2163295344895

+
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