4N7Y

Crystal structure of 14-3-3zeta in complex with a 8-carbon-linker cyclic peptide derived from ExoS


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.16 Å
  • R-Value Free: 0.256 
  • R-Value Work: 0.213 
  • R-Value Observed: 0.215 

wwPDB Validation   3D Report Full Report


This is version 2.0 of the entry. See complete history

Re-refinement Note

A newer entry is available that reflects an alternative modeling of the original data: 6RLZ


Literature

Constrained peptides with target-adapted cross-links as inhibitors of a pathogenic protein-protein interaction.

Glas, A.Bier, D.Hahne, G.Rademacher, C.Ottmann, C.Grossmann, T.N.

(2014) Angew Chem Int Ed Engl 53: 2489-2493

  • DOI: https://doi.org/10.1002/anie.201310082
  • Primary Citation of Related Structures:  
    4N7G, 4N7Y, 4N84

  • PubMed Abstract: 

    Bioactive conformations of peptides can be stabilized by macrocyclization, resulting in increased target affinity and activity. Such macrocyclic peptides proved useful as modulators of biological functions, in particular as inhibitors of protein-protein interactions (PPI). However, most peptide-derived PPI inhibitors involve stabilized α-helices, leaving a large number of secondary structures unaddressed. Herein, we present a rational approach towards stabilization of an irregular peptide structure, using hydrophobic cross-links that replace residues crucially involved in target binding. The molecular basis of this interaction was elucidated by X-ray crystallography and isothermal titration calorimetry. The resulting cross-linked peptides inhibit the interaction between human adaptor protein 14-3-3 and virulence factor exoenzyme S. Taking into consideration that irregular peptide structures participate widely in PPIs, this approach provides access to novel peptide-derived inhibitors.


  • Organizational Affiliation

    Chemical Genomics Centre of the Max Planck Society, Otto-Hahn-Strasse 15, 44227 Dortmund (Germany).


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
14-3-3 protein zeta/delta
A, B
235Homo sapiensMutation(s): 0 
Gene Names: NP_001129171.1YWHAZ
UniProt & NIH Common Fund Data Resources
Find proteins for P63104 (Homo sapiens)
Explore P63104 
Go to UniProtKB:  P63104
PHAROS:  P63104
GTEx:  ENSG00000164924 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP63104
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Exoenzyme S
C, D
11Pseudomonas aeruginosaMutation(s): 2 
UniProt
Find proteins for Q93SQ3 (Pseudomonas aeruginosa)
Explore Q93SQ3 
Go to UniProtKB:  Q93SQ3
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ93SQ3
Sequence Annotations
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  • Reference Sequence
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
MK8
Query on MK8
C, D
L-PEPTIDE LINKINGC7 H15 N O2LEU
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.16 Å
  • R-Value Free: 0.256 
  • R-Value Work: 0.213 
  • R-Value Observed: 0.215 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 72.51α = 90
b = 103.52β = 90
c = 114.04γ = 90
Software Package:
Software NamePurpose
XSCALEdata scaling
PHASERphasing
REFMACrefinement
PDB_EXTRACTdata extraction
XDSdata scaling
XDSdata reduction

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-02-19
    Type: Initial release
  • Version 1.1: 2014-03-12
    Changes: Database references
  • Version 2.0: 2023-11-15
    Changes: Atomic model, Data collection, Database references, Derived calculations