3UX0

Crystal structure of human 14-3-3 sigma in complex with TASK-3 peptide and stabilizer Fusicoccin H


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.75 Å
  • R-Value Free: 0.192 
  • R-Value Work: 0.151 
  • R-Value Observed: 0.153 

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Ligand Structure Quality Assessment 


This is version 1.1 of the entry. See complete history


Literature

A semisynthetic fusicoccane stabilizes a protein-protein interaction and enhances the expression of k(+) channels at the cell surface.

Anders, C.Higuchi, Y.Koschinsky, K.Bartel, M.Schumacher, B.Thiel, P.Nitta, H.Preisig-Muller, R.Schlichthorl, G.Renigunta, V.Ohkanda, J.Daut, J.Kato, N.Ottmann, C.

(2013) Chem Biol 20: 583-593

  • DOI: https://doi.org/10.1016/j.chembiol.2013.03.015
  • Primary Citation of Related Structures:  
    3P1N, 3P1O, 3P1P, 3P1Q, 3P1R, 3P1S, 3SMK, 3SML, 3SMM, 3SMN, 3SMO, 3SP5, 3SPR, 3UX0, 4FR3

  • PubMed Abstract: 

    Small-molecule stabilization of protein-protein interactions is an emerging field in chemical biology. We show how fusicoccanes, originally identified as fungal toxins acting on plants, promote the interaction of 14-3-3 proteins with the human potassium channel TASK-3 and present a semisynthetic fusicoccane derivative (FC-THF) that targets the 14-3-3 recognition motif (mode 3) in TASK-3. In the presence of FC-THF, the binding of 14-3-3 proteins to TASK-3 was increased 19-fold and protein crystallography provided the atomic details of the effects of FC-THF on this interaction. We also tested the functional effects of FC-THF on TASK channels heterologously expressed in Xenopus oocytes. Incubation with 10 μM FC-THF was found to promote the transport of TASK channels to the cell membrane, leading to a significantly higher density of channels at the surface membrane and increased potassium current.


  • Organizational Affiliation

    Chemical Genomics Centre of the Max-Planck-Society, 44227 Dortmund, Germany.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
14-3-3 protein sigma235Homo sapiensMutation(s): 0 
Gene Names: HME1SFN
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
TASK3 PHOSPHOPEPTIDEB [auth P]6Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for Q9NPC2 (Homo sapiens)
Explore Q9NPC2 
Go to UniProtKB:  Q9NPC2
PHAROS:  Q9NPC2
GTEx:  ENSG00000169427 
Entity Groups  
UniProt GroupQ9NPC2
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
0DV
Query on 0DV

Download Ideal Coordinates CCD File 
I [auth A](4R,5R,6R,6aS,9S,9aE,10aR)-5-hydroxy-9-(hydroxymethyl)-6,10a-dimethyl-3-(propan-2-yl)-1,2,4,5,6,6a,7,8,9,10a-decahydrod icyclopenta[a,d][8]annulen-4-yl alpha-D-gulopyranoside
C26 H42 O8
FQPATHNUIPAADA-HLKPNAMSSA-N
GOL
Query on GOL

Download Ideal Coordinates CCD File 
H [auth A]GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
CL
Query on CL

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

Download Ideal Coordinates CCD File 
C [auth A],
D [auth A],
E [auth A],
F [auth A]
MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
Modified Residues  2 Unique
IDChains TypeFormula2D DiagramParent
CSO
Query on CSO
A
L-PEPTIDE LINKINGC3 H7 N O3 SCYS
SEP
Query on SEP
B [auth P]L-PEPTIDE LINKINGC3 H8 N O6 PSER
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.75 Å
  • R-Value Free: 0.192 
  • R-Value Work: 0.151 
  • R-Value Observed: 0.153 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 81.9α = 90
b = 111.04β = 90
c = 62.35γ = 90
Software Package:
Software NamePurpose
XSCALEdata scaling
PHASERphasing
REFMACrefinement
PDB_EXTRACTdata extraction
XDSdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-01-02
    Type: Initial release
  • Version 1.1: 2013-05-01
    Changes: Database references