5ZJZ

Stapled-peptides tailored against initiation of translation


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.67 Å
  • R-Value Free: 0.212 
  • R-Value Work: 0.190 
  • R-Value Observed: 0.191 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Structural insights reveal a recognition feature for tailoring hydrocarbon stapled-peptides against the eukaryotic translation initiation factor 4E protein.

Lama, D.Liberatore, A.M.Frosi, Y.Nakhle, J.Tsomaia, N.Bashir, T.Lane, D.P.Brown, C.J.Verma, C.S.Auvin, S.

(2019) Chem Sci 10: 2489-2500

  • DOI: https://doi.org/10.1039/c8sc03759k
  • Primary Citation of Related Structures:  
    5ZJY, 5ZJZ, 5ZK5, 5ZK7, 5ZK9, 5ZML

  • PubMed Abstract: 

    Stapled-peptides have emerged as an exciting class of molecules which can modulate protein-protein interactions. We have used a structure-guided approach to rationally develop a set of hydrocarbon stapled-peptides with high binding affinities and residence times against the oncogenic eukaryotic translation initiation factor 4E (eIF4E) protein. Crystal structures of these peptides in complex with eIF4E show that they form specific interactions with a region on the protein-binding interface of eIF4E which is distinct from the other well-established canonical interactions. This recognition element is a major molecular determinant underlying the improved binding kinetics of these peptides with eIF4E. The interactions were further exploited by designing features in the peptides to attenuate disorder and increase helicity which collectively resulted in the generation of a distinct class of hydrocarbon stapled-peptides targeting eIF4E. This study details new insights into the molecular basis of stapled-peptide: eIF4E interactions and their exploitation to enhance promising lead molecules for the development of stapled-peptide compounds for oncology.


  • Organizational Affiliation

    Bioinformatics Institute , ASTAR (Agency for Science, Technology and Research) , 30 Biopolis Street, #07-01 Matrix , Singapore 138671 . Email: chandra@bii.a-star.edu.sg ; Tel: +65 6478 8273.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Eukaryotic translation initiation factor 4E191Homo 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

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Eukaryotic translation initiation factor 4 gamma 115Homo sapiensMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
MGT
Query on MGT

Download Ideal Coordinates CCD File 
C [auth A]7N-METHYL-8-HYDROGUANOSINE-5'-TRIPHOSPHATE
C11 H20 N5 O14 P3
BUJQMJUTTBGELS-KQYNXXCUSA-N
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: 1.67 Å
  • R-Value Free: 0.212 
  • R-Value Work: 0.190 
  • R-Value Observed: 0.191 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 91.27α = 90
b = 38.3β = 122.74
c = 78.93γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
XDSdata reduction
XDSdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2019-02-20
    Type: Initial release
  • Version 1.1: 2019-04-03
    Changes: Data collection, Database references
  • Version 1.2: 2023-11-22
    Changes: Data collection, Database references, Refinement description