2QC6

Protein kinase CK2 in complex with DBC


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.85 Å
  • R-Value Free: 0.268 
  • R-Value Work: 0.214 
  • R-Value Observed: 0.217 

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Ligand Structure Quality Assessment 


This is version 1.1 of the entry. See complete history


Literature

Coumarin as attractive casein kinase 2 (CK2) inhibitor scaffold: an integrate approach to elucidate the putative binding motif and explain structure-activity relationships.

Chilin, A.Battistutta, R.Bortolato, A.Cozza, G.Zanatta, S.Poletto, G.Mazzorana, M.Zagotto, G.Uriarte, E.Guiotto, A.Pinna, L.A.Meggio, F.Moro, S.

(2008) J Med Chem 51: 752-759

  • DOI: https://doi.org/10.1021/jm070909t
  • Primary Citation of Related Structures:  
    2QC6

  • PubMed Abstract: 

    Casein kinase 2 (CK2) is an ubiquitous, essential, and highly pleiotropic protein kinase whose abnormally high constitutive activity is suspected to underlie its pathogenic potential in neoplasia and other diseases. Recently, using different virtual screening approaches, we have identified several novel CK2 inhibitors. In particular, we have discovered that coumarin moiety can be considered an attractive CK2 inhibitor scaffold. In the present work, we have synthetized and tested a small library of coumarins (more than 60), rationalizing the observed structure-activity relationship. Moreover, the most promising inhibitor, 3,8-dibromo-7-hydroxy-4-methylchromen-2-one (DBC), has been also crystallized in complex with CK2, and the experimental binding mode has been used to derive a linear interaction energy (LIE) model.


  • Organizational Affiliation

    Dipartimento di Scienze Farmaceutiche, Università di Padova, via Marzolo 5, Padova, Italy.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Casein kinase II subunit alpha332Zea maysMutation(s): 1 
Gene Names: ACK2
EC: 2.7.11.1
UniProt
Find proteins for P28523 (Zea mays)
Explore P28523 
Go to UniProtKB:  P28523
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP28523
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
G12
Query on G12

Download Ideal Coordinates CCD File 
B [auth A]3,8-DIBROMO-7-HYDROXY-4-METHYL-2H-CHROMEN-2-ONE
C10 H6 Br2 O3
MSOLROYRAHCJNK-UHFFFAOYSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
CSO
Query on CSO
A
L-PEPTIDE LINKINGC3 H7 N O3 SCYS
Binding Affinity Annotations 
IDSourceBinding Affinity
DBC PDBBind:  2QC6 IC50: 100 (nM) from 1 assay(s)
G12 Binding MOAD:  2QC6 IC50: 100 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.85 Å
  • R-Value Free: 0.268 
  • R-Value Work: 0.214 
  • R-Value Observed: 0.217 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 141.676α = 90
b = 60.252β = 103
c = 44.901γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
MAR345dtbdata collection
MOSFLMdata reduction
SCALAdata scaling
AMoREphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-02-26
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance