1OM1

Crystal structure of maize CK2 alpha in complex with IQA


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.68 Å
  • R-Value Free: 0.227 
  • R-Value Work: 0.206 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Biochemical and three-dimensional-structural study of the specific inhibition of protein kinase CK2 by [5-oxo-5,6-dihydroindolo-(1,2-a)quinazolin-7-yl]acetic acid (IQA).

Sarno, S.de Moliner, E.Ruzzene, M.Pagano, M.A.Battistutta, R.Bain, J.Fabbro, D.Schoepfer, J.Elliott, M.Furet, P.Meggio, F.Zanotti, G.Pinna, L.A.

(2003) Biochem J 374: 639-646

  • DOI: https://doi.org/10.1042/BJ20030674
  • Primary Citation of Related Structures:  
    1OM1

  • PubMed Abstract: 

    IQA [[5-oxo-5,6-dihydro-indolo(1,2-a)quinazolin-7-yl]acetic acid] is a novel ATP/GTP site-directed inhibitor of CK2 ('casein kinase 2'), a pleiotropic and constitutively active protein kinase whose activity is abnormally high in transformed cells. The K (i) value of IQA (0.17 microM) is lower than those of other CK2 inhibitors reported so far. Tested at 10 microM concentration in the presence of 100 microM ATP, IQA almost suppresses CK2 activity in vitro, whereas it is ineffective or weakly effective on a panel of 44 protein kinases and on phosphoinositide 3-kinase. In comparison, other CK2 inhibitors, notably apigenin and quercetin, are more promiscuous. The in vivo efficacy of IQA has been assessed by using the fact that treatment of Jurkat cells with IQA inhibits endogenous CK2 in a dose-dependent manner. IQA has been co-crystallized with maize CK2alpha, which is >70% identical with its human homologue, and the structure of the complex has been determined at 1.68 A (1 A=0.1 nm) resolution. The inhibitor lies in the same plane occupied by the purine moiety of ATP with its more hydrophobic side facing the hinge region. Major contributions to the interaction are provided by hydrophobic forces and non-polar interactions involving the aromatic portion of the inhibitor and the hydrophobic residues surrounding the ATP-binding pocket, with special reference to the side chains of V53 (Val53), I66, M163 and I174. Consequently, mutants of human CK2alpha in which either V66 (the homologue of maize CK2alpha I66) or I174 is replaced by alanine are considerably less sensitive to IQA inhibition when compared with wild-type. These results provide new tools for deciphering the enigmatic role of CK2 in living cells and may pave the way for the development of drugs depending on CK2 activity.


  • Organizational Affiliation

    Venetian Institute for Molecular Medicine (VIMM), University of Padova, 35121 Padova, Italy.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Casein kinase II, alpha chain332Zea 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
IQA
Query on IQA

Download Ideal Coordinates CCD File 
B [auth A](5-OXO-5,6-DIHYDRO-INDOLO[1,2-A]QUINAZOLIN-7-YL)-ACETIC ACID
C17 H12 N2 O3
INSBKYCYLCEBOD-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
IQA PDBBind:  1OM1 Ki: 170 (nM) from 1 assay(s)
Binding MOAD:  1OM1 Ki: 170 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.68 Å
  • R-Value Free: 0.227 
  • R-Value Work: 0.206 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 141.524α = 90
b = 60.276β = 102.63
c = 44.546γ = 90
Software Package:
Software NamePurpose
CNSrefinement
MAR345data collection
CCP4data scaling
CNSphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-02-24
    Type: Initial release
  • Version 1.1: 2008-04-29
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2017-10-11
    Changes: Refinement description
  • Version 1.4: 2024-02-14
    Changes: Data collection, Database references, Derived calculations