3E3B

Crystal structure of catalytic subunit of human protein kinase CK2alpha prime with a potent indazole-derivative inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.20 Å
  • R-Value Free: 0.274 
  • R-Value Work: 0.248 
  • R-Value Observed: 0.268 

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This is version 1.2 of the entry. See complete history


Literature

Structure of human protein kinase CK2alpha2 with a potent indazole-derivative inhibitor

Nakaniwa, T.Kinoshita, T.Sekiguchi, Y.Tada, T.Nakanishi, I.Kitaura, K.Suzuki, Y.Ohno, H.Hirasawa, A.Tsujimoto, G.

(2009) Acta Crystallogr Sect F Struct Biol Cryst Commun 65: 75-79

  • DOI: https://doi.org/10.1107/S1744309108043194
  • Primary Citation of Related Structures:  
    3E3B

  • PubMed Abstract: 

    Casein kinase 2 (CK2) is a serine/threonine kinase that functions as a heterotetramer composed of two catalytic subunits (CK2alpha1 or CK2alpha2) and two regulatory subunits (CK2beta). The two isozymes CK2alpha1 and CK2alpha2 play distinguishable roles in healthy subjects and in patients with diseases such as cancer, respectively. In order to develop novel CK2alpha1-selective inhibitors, the crystal structure of human CK2alpha2 (hCK2alpha2) complexed with a potent CK2alpha inhibitor which binds to the active site of hCK2alpha2 was determined and compared with that of human CK2alpha1. While the two isozymes exhibited a high similarity with regard to the active site, the largest structural difference between the isoforms occurred in the beta4-beta5 loop responsible for the CK2alpha-CK2beta interface. The top of the N-terminal segment interacted with the beta4-beta5 loop via a hydrogen bond in hCK2alpha2 but not in hCK2alpha1. Thus, the CK2alpha-CK2beta interface is a likely target candidate for the production of selective CK2alpha1 inhibitors.


  • Organizational Affiliation

    Graduate School of Sciences, Osaka Prefecture University, Osaka 599-8530, Japan.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Casein kinase II subunit alpha'A [auth X]339Homo sapiensMutation(s): 0 
Gene Names: CSNK2A2CK2A2
EC: 2.7.11.1
UniProt & NIH Common Fund Data Resources
Find proteins for P19784 (Homo sapiens)
Explore P19784 
Go to UniProtKB:  P19784
PHAROS:  P19784
GTEx:  ENSG00000070770 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP19784
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
CCK
Query on CCK

Download Ideal Coordinates CCD File 
B [auth X][1-(6-{6-[(1-methylethyl)amino]-1H-indazol-1-yl}pyrazin-2-yl)-1H-pyrrol-3-yl]acetic acid
C20 H20 N6 O2
BBYRUZKRFAIQSR-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
CCK PDBBind:  3E3B IC50: 11 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.20 Å
  • R-Value Free: 0.274 
  • R-Value Work: 0.248 
  • R-Value Observed: 0.268 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 69.813α = 90
b = 102.126β = 90
c = 46.618γ = 90
Software Package:
Software NamePurpose
ADSCdata collection
MOLREPphasing
CNXrefinement
HKL-2000data reduction
HKL-2000data 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: 2009-03-03
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-11-01
    Changes: Data collection, Database references, Derived calculations, Refinement description