1M2P

Crystal structure of 1,8-di-hydroxy-4-nitro-anthraquinone/CK2 kinase complex


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.243 
  • R-Value Work: 0.223 
  • R-Value Observed: 0.223 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Inhibition of protein kinase CK2 by anthraquinone-related compounds. A structural insight

De Moliner, E.Moro, S.Sarno, S.Zagotto, G.Zanotti, G.Pinna, L.A.Battistutta, R.

(2003) J Biol Chem 278: 1831-1836

  • DOI: https://doi.org/10.1074/jbc.M209367200
  • Primary Citation of Related Structures:  
    1M2P, 1M2Q, 1M2R

  • PubMed Abstract: 

    Protein kinases play key roles in signal transduction and therefore are among the most attractive targets for drug design. The pharmacological aptitude of protein kinase inhibitors is highlighted by the observation that various diseases with special reference to cancer are because of the abnormal expression/activity of individual kinases. The resolution of the three-dimensional structure of the target kinase in complex with inhibitors is often the starting point for the rational design of this kind of drugs, some of which are already in advanced clinical trial or even in clinical practice. Here we present and discuss three new crystal structures of ATP site-directed inhibitors in complex with "casein kinase-2" (CK2), a constitutively active protein kinase implicated in a variety of cellular functions and misfunctions. With the help of theoretical calculations, we disclose some key features underlying the inhibitory efficiency of anthraquinone derivatives, outlining three different binding modes into the active site. In particular, we show that a nitro group in a hydroxyanthraquinone scaffold decreases the inhibitory constants K(i) because of electron-withdrawing and resonance effects that enhance the polarization of hydroxylic substituents in paraposition.


  • Organizational Affiliation

    Department of Organic Chemistry, University of Padova, Padova 35131, Italy.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Casein kinase II, alpha chain325Zea maysMutation(s): 0 
EC: 2.7.1.37
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
HNA
Query on HNA

Download Ideal Coordinates CCD File 
B [auth A]1,8-DI-HYDROXY-4-NITRO-ANTHRAQUINONE
C14 H7 N O6
RIYCICFDXLNQPV-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
HNA PDBBind:  1M2P Ki: 780 (nM) from 1 assay(s)
BindingDB:  1M2P Ki: 780 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.243 
  • R-Value Work: 0.223 
  • R-Value Observed: 0.223 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 142.09α = 90
b = 60.55β = 102.84
c = 44.98γ = 90
Software Package:
Software NamePurpose
MOSFLMdata reduction
SCALAdata scaling
AMoREphasing
CNSrefinement
CCP4data scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2003-06-17
    Type: Initial release
  • Version 1.1: 2008-04-28
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2024-02-14
    Changes: Data collection, Database references, Derived calculations