4BEA

Crystal Structure of eIF4E in Complex with a Stapled Peptide Derivative


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.57 Å
  • R-Value Free: 0.266 
  • R-Value Work: 0.220 
  • R-Value Observed: 0.222 

wwPDB Validation   3D Report Full Report


This is version 2.1 of the entry. See complete history


Literature

Rational Optimization of Conformational Effects Induced by Hydrocarbon Staples in Peptides and Their Binding Interfaces.

Lama, D.Quah, S.T.Verma, C.S.Lakshminarayanan, R.Beuerman, R.W.Lane, D.P.Brown, C.J.

(2013) Sci Rep 3: 3451

  • DOI: https://doi.org/10.1038/srep03451
  • Primary Citation of Related Structures:  
    4BEA

  • PubMed Abstract: 

    eIF4E is frequently over-expressed in different cancers and causes increased translation of oncogenic proteins via deregulated cap-dependent translation. Inhibitors of the eIF4E:eIF4G interactions represent an approach that would normalize cap-dependent translation. Stapled peptides represent an emerging class of therapeutics that can target protein: protein interactions. We present here molecular dynamics simulations for a set of rationally designed stapled peptides in solution and in complex with eIF4E, supported with biophysical and crystallographic data. Clustering of the simulated structures revealed the favoured conformational states of the stapled peptides in their bound or free forms in solution. Identifying these populations has allowed us to design peptides with improved affinities by introducing mutations into the peptide sequence to alter their conformational distributions. These studies emphasise the effects that engineered mutations have on the conformations of free and bound peptides, and illustrate that both states must be considered in efforts to attain high affinity binding.


  • Organizational Affiliation

    1] Bioinformatics Institute, A*STAR (Agency for Science, Technology and Research), 30 Biopolis Street, #07-01 Matrix, Singapore 138671 [2].


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Eukaryotic translation initiation factor 4E217Homo sapiensMutation(s): 0 
Gene Names: EIF4EEIF4EL1EIF4F
UniProt & NIH Common Fund Data Resources
Find proteins for P06730 (Homo sapiens)
Explore P06730 
Go to UniProtKB:  P06730
PHAROS:  P06730
GTEx:  ENSG00000151247 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP06730
Sequence Annotations
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  • Reference Sequence

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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
STAPLED EIF4E INTERACTING PEPTIDE13synthetic constructMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
MK8
Query on MK8
B
L-PEPTIDE LINKINGC7 H15 N O2LEU
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.57 Å
  • R-Value Free: 0.266 
  • R-Value Work: 0.220 
  • R-Value Observed: 0.222 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 38.301α = 90
b = 91.677β = 90
c = 137.908γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
PROTEUM2data reduction
PROTEUM2data scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-12-11
    Type: Initial release
  • Version 1.1: 2014-01-08
    Changes: Database references
  • Version 1.2: 2018-04-04
    Changes: Data collection
  • Version 2.0: 2023-03-15
    Changes: Atomic model, Database references, Derived calculations, Non-polymer description, Other, Polymer sequence, Source and taxonomy, Structure summary
  • Version 2.1: 2024-02-07
    Changes: Data collection, Refinement description