[English] 日本語
Yorodumi
- PDB-8sx4: Crystal Structure of eIF4e in complex with Compound 7n -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8sx4
TitleCrystal Structure of eIF4e in complex with Compound 7n
ComponentsEukaryotic translation initiation factor 4EEIF4E
KeywordsTRANSLATION / eIF4e / translation initiation inhibitor
Function / homology
Function and homology information


Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S / : / eukaryotic initiation factor 4G binding / regulation of translation at postsynapse, modulating synaptic transmission / RNA cap binding / chromatoid body / eukaryotic translation initiation factor 4F complex / Z-decay: degradation of maternal mRNAs by zygotically expressed factors / mRNA cap binding / Deadenylation of mRNA ...Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S / : / eukaryotic initiation factor 4G binding / regulation of translation at postsynapse, modulating synaptic transmission / RNA cap binding / chromatoid body / eukaryotic translation initiation factor 4F complex / Z-decay: degradation of maternal mRNAs by zygotically expressed factors / mRNA cap binding / Deadenylation of mRNA / Transport of the SLBP independent Mature mRNA / RNA 7-methylguanosine cap binding / 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 / Ribosomal scanning and start codon recognition / Translation initiation complex formation / stem cell population maintenance / mTORC1-mediated signalling / GTP hydrolysis and joining of the 60S ribosomal subunit / negative regulation of neuron differentiation / L13a-mediated translational silencing of Ceruloplasmin expression / behavioral fear response / mRNA export from nucleus / translational initiation / translation initiation factor activity / positive regulation of mitotic cell cycle / cellular response to dexamethasone stimulus / P-body / neuron differentiation / G1/S transition of mitotic cell cycle / ISG15 antiviral mechanism / cytoplasmic stress granule / cytoplasmic ribonucleoprotein granule / regulation of translation / postsynapse / DNA-binding transcription factor binding / negative regulation of translation / nuclear speck / glutamatergic synapse / perinuclear region of cytoplasm / enzyme binding / RNA binding / extracellular exosome / nucleus / cytosol / cytoplasm
Similarity search - Function
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
Similarity search - Domain/homology
7N-METHYL-8-HYDROGUANOSINE-5'-DIPHOSPHATE / Chem-WXL / Eukaryotic translation initiation factor 4E
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.986 Å
AuthorsMeagher, J.L. / Stuckey, J.A.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)GM132341 United States
Citation
Journal: J.Med.Chem. / Year: 2023
Title: Design of Cell-Permeable Inhibitors of Eukaryotic Translation Initiation Factor 4E (eIF4E) for Inhibiting Aberrant Cap-Dependent Translation in Cancer.
Authors: Cardenas, E.L. / O'Rourke, R.L. / Menon, A. / Meagher, J. / Stuckey, J. / Garner, A.L.
#1: Journal: Biorxiv / Year: 2023
Title: Design of Cell-Permeable Inhibitors of Eukaryotic Translation Initiation Factor 4E (eIF4E) for Inhibiting Aberrant Cap-Dependent Translation in Cancer.
Authors: Cardenas, E.L. / O'Rourke, R.L. / Menon, A. / Meagher, J. / Stuckey, J. / Garner, A.L.
History
DepositionMay 19, 2023Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 21, 2023Provider: repository / Type: Initial release
Revision 1.1Aug 23, 2023Group: Data collection / Database references
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / citation / citation_author

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

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


Theoretical massNumber of molelcules
Total (without water)45,4904
Polymers44,5812
Non-polymers9092
Water2,918162
1
A: Eukaryotic translation initiation factor 4E
hetero molecules


Theoretical massNumber of molelcules
Total (without water)22,7402
Polymers22,2901
Non-polymers4501
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: Eukaryotic translation initiation factor 4E
hetero molecules


Theoretical massNumber of molelcules
Total (without water)22,7502
Polymers22,2901
Non-polymers4591
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)49.125, 74.328, 51.877
Angle α, β, γ (deg.)90.00, 97.13, 90.00
Int Tables number4
Space group name H-MP1211

-
Components

#1: Protein Eukaryotic translation initiation factor 4E / EIF4E / eIF4E / eIF-4F 25 kDa subunit / mRNA cap-binding protein


Mass: 22290.334 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: EIF4E, EIF4EL1, EIF4F / Production host: Escherichia coli (E. coli) / References: UniProt: P06730
#2: Chemical ChemComp-WXL / [(~{Z})-4-[2-azanyl-7-[(5-chloranyl-1~{H}-indol-2-yl)methyl]-6-oxidanylidene-1~{H}-purin-9-yl]but-2-enyl]phosphonic acid


Mass: 449.808 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C18H19ClN6O4P / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-M7G / 7N-METHYL-8-HYDROGUANOSINE-5'-DIPHOSPHATE


Mass: 459.243 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C11H19N5O11P2
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 162 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.11 Å3/Da / Density % sol: 41.65 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop
Details: 16-26% Peg 3350, 0.1 M MES pH 6.0, 10% isopropanol and 2 mM CaCl2

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 21-ID-D / Wavelength: 1.1276 Å
DetectorType: DECTRIS EIGER X 9M / Detector: PIXEL / Date: Jul 26, 2022
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.1276 Å / Relative weight: 1
ReflectionResolution: 1.986→50 Å / Num. obs: 24897 / % possible obs: 98 % / Redundancy: 5.2 % / CC1/2: 0.987 / CC star: 0.997 / Rmerge(I) obs: 0.074 / Rpim(I) all: 0.035 / Rrim(I) all: 0.083 / Χ2: 0.877 / Net I/σ(I): 10.1
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique obsCC1/2CC starRpim(I) allRrim(I) allΧ2% possible all
2-2.034.20.38312450.8730.9660.2040.4360.71299.2
2.03-2.074.30.33412530.8990.9730.1750.3790.76198.7
2.07-2.114.50.30512270.9150.9780.1530.3420.82399.3
2.11-2.154.60.29612580.9120.9770.1470.3320.87897.7
2.15-2.24.50.2512180.9450.9860.1260.2810.91597.4
2.2-2.254.40.25312250.9430.9850.1290.2850.93295.2
2.25-2.314.40.21511980.940.9840.1110.2430.95897.3
2.31-2.375.40.20712750.9760.9940.0960.2280.93799.5
2.37-2.445.70.20212480.9770.9940.0910.2220.91599.5
2.44-2.525.80.19812650.9590.9890.0890.2180.88999.5
2.52-2.615.90.17912650.9640.9910.0810.1970.92699.1
2.61-2.7160.15212710.9850.9960.0680.1670.90499.1
2.71-2.845.90.12812160.9770.9940.0580.1410.92798.4
2.84-2.995.80.10712410.9810.9950.0490.1180.92998.4
2.99-3.175.70.0912440.9820.9950.0420.0990.96497.7
3.17-3.425.40.07212630.9860.9960.0350.080.96297.7
3.42-3.7650.05912390.990.9980.0290.0660.91496.6
3.76-4.314.40.04911580.9910.9980.0260.0560.8691.2
4.31-5.435.50.04512730.9950.9990.0220.050.79998.9
5.43-506.50.04313150.99810.0180.0460.63699.8

-
Processing

Software
NameVersionClassification
BUSTER2.10.4 (17-FEB-2023)refinement
HKL-2000data scaling
HKL-2000data reduction
PHASESphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.986→37.81 Å / Cor.coef. Fo:Fc: 0.935 / Cor.coef. Fo:Fc free: 0.909 / SU R Cruickshank DPI: 0.208 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.206 / SU Rfree Blow DPI: 0.174 / SU Rfree Cruickshank DPI: 0.176
RfactorNum. reflection% reflectionSelection details
Rfree0.2428 1310 5.33 %RANDOM
Rwork0.1974 ---
obs0.1998 24565 95.9 %-
Displacement parametersBiso mean: 26.48 Å2
Baniso -1Baniso -2Baniso -3
1-0.152 Å20 Å2-1.083 Å2
2---0.0442 Å20 Å2
3----0.1078 Å2
Refine analyzeLuzzati coordinate error obs: 0.23 Å
Refinement stepCycle: LAST / Resolution: 1.986→37.81 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2990 0 59 163 3212
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.0083129HARMONIC2
X-RAY DIFFRACTIONt_angle_deg0.874245HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d1093SINUSOIDAL2
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes
X-RAY DIFFRACTIONt_gen_planes559HARMONIC5
X-RAY DIFFRACTIONt_it3129HARMONIC10
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_omega_torsion3.34
X-RAY DIFFRACTIONt_other_torsion16.1
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_chiral_improper_torsion387SEMIHARMONIC5
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_contact2532SEMIHARMONIC4
LS refinement shellResolution: 1.99→2.01 Å / Total num. of bins used: 51
RfactorNum. reflection% reflection
Rfree0.2585 -4.88 %
Rwork0.2219 468 -
all0.2238 492 -
obs--64.21 %

+
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