4BFP

Crystal structure of human tankyrase 2 in complex with WIKI4


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.250 
  • R-Value Work: 0.202 
  • R-Value Observed: 0.204 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.5 of the entry. See complete history


Literature

Structural Basis and Selectivity of Tankyrase Inhibition by a Wnt Signaling Inhibitor Wiki4

Haikarainen, T.Venkannagari, H.Narwal, M.Obaji, E.Lee, H.Nkizinkiko, Y.Lehtio, L.

(2013) PLoS One 8: 65404

  • DOI: https://doi.org/10.1371/journal.pone.0065404
  • Primary Citation of Related Structures:  
    4BFP

  • PubMed Abstract: 

    Recently a novel inhibitor of Wnt signaling was discovered. The compound, WIKI4, was found to act through tankyrase inhibition and regulate β-catenin levels in many cancer cell lines and human embryonic stem cells. Here we confirm that WIKI4 is a high potency tankyrase inhibitor and that it selectively inhibits tankyrases over other ARTD enzymes tested. The binding mode of the compound to tankyrase 2 was determined by protein X-ray crystallography to 2.4 Å resolution. The structure revealed a novel binding mode to the adenosine subsite of the donor NAD(+) binding groove of the catalytic domain. Our results form a structural basis for further development of potent and selective tankyrase inhibitors based on the WIKI4 scaffold.


  • Organizational Affiliation

    Biocenter Oulu, Department of Biochemistry, University of Oulu, Oulu, Finland.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
TANKYRASE-2
A, B
240Homo sapiensMutation(s): 0 
EC: 2.4.2.30
UniProt & NIH Common Fund Data Resources
Find proteins for Q9H2K2 (Homo sapiens)
Explore Q9H2K2 
Go to UniProtKB:  Q9H2K2
PHAROS:  Q9H2K2
GTEx:  ENSG00000107854 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9H2K2
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
SWY
Query on SWY

Download Ideal Coordinates CCD File 
C [auth A],
G [auth B]
2-[3-[[4-(4-methoxyphenyl)-5-pyridin-4-yl-1,2,4-triazol-3-yl]sulfanyl]propyl]benzo[de]isoquinoline-1,3-dione
C29 H23 N5 O3 S
RNUXIZKXJOGYQP-UHFFFAOYSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
D [auth A],
E [auth A],
H [auth B],
I [auth B]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
ZN
Query on ZN

Download Ideal Coordinates CCD File 
F [auth A],
J [auth B]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
SWY PDBBind:  4BFP IC50: 15 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.250 
  • R-Value Work: 0.202 
  • R-Value Observed: 0.204 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 88.96α = 90
b = 93.17β = 90
c = 117.05γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
XSCALEdata 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: 2013-06-19
    Type: Initial release
  • Version 1.1: 2013-06-26
    Changes: Database references
  • Version 1.2: 2014-09-10
    Changes: Database references
  • Version 1.3: 2015-04-01
    Changes: Database references
  • Version 1.4: 2019-01-30
    Changes: Data collection, Experimental preparation
  • Version 1.5: 2019-02-06
    Changes: Data collection, Experimental preparation