5N5W

14-3-3 sigma in complex with TAZ pS89 peptide and fragment NV3


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.37 Å
  • R-Value Free: 0.165 
  • R-Value Work: 0.144 
  • R-Value Observed: 0.145 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Identification of Two Secondary Ligand Binding Sites in 14-3-3 Proteins Using Fragment Screening.

Sijbesma, E.Skora, L.Leysen, S.Brunsveld, L.Koch, U.Nussbaumer, P.Jahnke, W.Ottmann, C.

(2017) Biochemistry 56: 3972-3982

  • DOI: https://doi.org/10.1021/acs.biochem.7b00153
  • Primary Citation of Related Structures:  
    5N5R, 5N5T, 5N5W, 5N75

  • PubMed Abstract: 

    Proteins typically interact with multiple binding partners, and often different parts of their surfaces are employed to establish these protein-protein interactions (PPIs). Members of the class of 14-3-3 adapter proteins bind to several hundred other proteins in the cell. Multiple small molecules for the modulation of 14-3-3 PPIs have been disclosed; however, they all target the conserved phosphopeptide binding channel, so that selectivity is difficult to achieve. Here we report on the discovery of two individual secondary binding sites that have been identified by combining nuclear magnetic resonance-based fragment screening and X-ray crystallography. The two pockets that these fragments occupy are part of at least three physiologically relevant and structurally characterized 14-3-3 PPI interfaces, including those with serotonin N-acetyltransferase and plant transcription factor FT. In addition, the high degree of conservation of the two sites implies their relevance for 14-3-3 PPIs. This first identification of secondary sites on 14-3-3 proteins bound by small molecule ligands might facilitate the development of new chemical tool compounds for more selective PPI modulation.


  • Organizational Affiliation

    Department of Biomedical Engineering, Laboratory of Chemical Biology, and Institute for Complex Molecular Systems, Eindhoven University of Technology , P.O. Box 513, 5600 MB Eindhoven, The Netherlands.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
14-3-3 protein sigma236Homo sapiensMutation(s): 0 
Gene Names: SFNHME1
UniProt & NIH Common Fund Data Resources
Find proteins for P31947 (Homo sapiens)
Explore P31947 
Go to UniProtKB:  P31947
PHAROS:  P31947
GTEx:  ENSG00000175793 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP31947
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
TAZ pS89 peptideB [auth P]10Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for Q9GZV5 (Homo sapiens)
Explore Q9GZV5 
Go to UniProtKB:  Q9GZV5
PHAROS:  Q9GZV5
GTEx:  ENSG00000018408 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9GZV5
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
8OE
Query on 8OE

Download Ideal Coordinates CCD File 
I [auth A]4-[3,5-bis(chloranyl)pyridin-2-yl]oxyaniline
C11 H8 Cl2 N2 O
PGVMWEHPHKWCFC-UHFFFAOYSA-N
CA
Query on CA

Download Ideal Coordinates CCD File 
G [auth A]CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
CL
Query on CL

Download Ideal Coordinates CCD File 
E [auth A],
F [auth A]
CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
MG
Query on MG

Download Ideal Coordinates CCD File 
C [auth A],
D [auth A],
H [auth A]
MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
SEP
Query on SEP
B [auth P]L-PEPTIDE LINKINGC3 H8 N O6 PSER
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.37 Å
  • R-Value Free: 0.165 
  • R-Value Work: 0.144 
  • R-Value Observed: 0.145 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 81.293α = 90
b = 112.286β = 90
c = 62.506γ = 90
Software Package:
Software NamePurpose
Aimlessdata scaling
PHENIXrefinement
PDB_EXTRACTdata extraction
XDSdata reduction
BUSTERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2017-07-19
    Type: Initial release
  • Version 1.1: 2017-08-09
    Changes: Database references
  • Version 1.2: 2024-01-17
    Changes: Data collection, Database references, Derived calculations, Refinement description