4HLF

Crystal structure of Tankyrase 2 in complex with 7,3',4'-Trihydroxyflavone


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.15 Å
  • R-Value Free: 0.211 
  • R-Value Work: 0.170 
  • R-Value Observed: 0.172 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Screening and structural analysis of flavones inhibiting tankyrases.

Narwal, M.Haikarainen, T.Fallarero, A.Vuorela, P.M.Lehtio, L.

(2013) J Med Chem 56: 3507-3517

  • DOI: https://doi.org/10.1021/jm3018783
  • Primary Citation of Related Structures:  
    4HKI, 4HKK, 4HKN, 4HL5, 4HLF, 4HLG, 4HLH, 4HLK, 4HLM, 4HMH

  • PubMed Abstract: 

    Flavonoids are known for their beneficial effects on human health, and therefore the therapeutic potential of these compounds have been extensively studied. Flavone has been previously identified as a tankyrase inhibitor, and to further elucidate whether tankyrases would be inhibited by other flavonoids, we performed a systematic screening of tankyrase 2 inhibitory activity using 500 natural and naturally derived flavonoids covering nine different flavonoid classes. All identified tankyrase inhibitors were flavones. We report crystal structures of all the hit compounds in complex with the catalytic domain of human tankyrase 2. Flavone derivatives in all 10 crystal structures bind to the nicotinamide binding site of tankyrase 2. Potencies of the active flavones toward tankyrases vary between 50 nM and 1.1 μM, and flavones show up to 200-fold selectivity for tankyrases over ARTD1. The molecular details of the interactions revealed by cocrystal structures efficiently describe the properties of potent flavone derivatives inhibiting tankyrases.


  • Organizational Affiliation

    Biocenter Oulu and 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-2A,
C [auth B]
191Homo sapiensMutation(s): 0 
Gene Names: TNKS2PARP5BTANK2TNKL
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
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Tankyrase-2B [auth C],
D
49Homo sapiensMutation(s): 0 
Gene Names: TNKS2PARP5BTANK2TNKL
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 5 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
15Z
Query on 15Z

Download Ideal Coordinates CCD File 
I [auth A],
N [auth B]
2-(3,4-dihydroxyphenyl)-7-hydroxy-4H-chromen-4-one
C15 H10 O5
PVFGJHYLIHMCQD-UHFFFAOYSA-N
PEG
Query on PEG

Download Ideal Coordinates CCD File 
H [auth A],
P [auth D]
DI(HYDROXYETHYL)ETHER
C4 H10 O3
MTHSVFCYNBDYFN-UHFFFAOYSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
F [auth A],
G [auth A],
L [auth B],
O [auth D]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
GOL
Query on GOL

Download Ideal Coordinates CCD File 
J [auth C],
M [auth B]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
E [auth A],
K [auth B]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
15Z PDBBind:  4HLF IC50: 870 (nM) from 1 assay(s)
BindingDB:  4HLF IC50: min: 630, max: 870 (nM) from 2 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.15 Å
  • R-Value Free: 0.211 
  • R-Value Work: 0.170 
  • R-Value Observed: 0.172 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 91.4α = 90
b = 97.95β = 90
c = 118.76γ = 90
Software Package:
Software NamePurpose
MxCuBEdata collection
MOLREPphasing
REFMACrefinement
XDSdata reduction
XSCALEdata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-10-31
    Type: Initial release
  • Version 1.1: 2013-05-08
    Changes: Database references
  • Version 1.2: 2013-05-22
    Changes: Database references
  • Version 1.3: 2023-09-20
    Changes: Data collection, Database references, Derived calculations, Refinement description