6HMD

STRUCTURE OF PROTEIN KINASE CK2 CATALYTIC SUBUNIT (ISOFORM CK2ALPHA'; CSNK2A2 gene product) IN COMPLEX WITH THE INDENOINDOLE-TYPE INHIBITOR AR18


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.00 Å
  • R-Value Free: 0.172 
  • R-Value Work: 0.149 
  • R-Value Observed: 0.150 

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This is version 1.2 of the entry. See complete history


Literature

Diacritic Binding of an Indenoindole Inhibitor by CK2 alpha Paralogs Explored by a Reliable Path to Atomic Resolution CK2 alpha ' Structures.

Lindenblatt, D.Nickelsen, A.Applegate, V.M.Hochscherf, J.Witulski, B.Bouaziz, Z.Marminon, C.Bretner, M.Le Borgne, M.Jose, J.Niefind, K.

(2019) ACS Omega 4: 5471-5478

  • DOI: https://doi.org/10.1021/acsomega.8b03415
  • Primary Citation of Related Structures:  
    6HBN, 6HMB, 6HMC, 6HMD, 6HME, 6HMQ

  • PubMed Abstract: 

    CK2α and CK2α' are the two isoforms of the catalytic subunit of human protein kinase CK2, an important target for cancer therapy. They have similar, albeit not identical functional and structural properties, and were occasionally reported to be inhibited with distinct efficacies by certain ATP-competitive ligands. Here, we present THN27, an indeno[1,2- b ]indole derivative, as a further inhibitor with basal isoform selectivity. The selectivity disappears when measured using CK2α/CK2α' complexes with CK2β, the regulatory CK2 subunit. Co-crystal structures of THN27 with CK2α and CK2α' reveal that subtle differences in the conformational variability of the interdomain hinge region are correlated with the observed effect. In the case of CK2α', a crystallographically problematic protein so far, this comparative structural analysis required the development of an experimental strategy that finally enables atomic resolution structure determinations with ab initio phasing of potentially any ATP-competitive CK2 inhibitor and possibly many non-ATP-competitive ligands as well bound to CK2α'.


  • Organizational Affiliation

    Department für Chemie, Institut für Biochemie, Universität zu Köln, Zülpicher Straße 47, D-50674 Köln, Germany.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Casein kinase II subunit alpha'365Homo sapiensMutation(s): 1 
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
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.00 Å
  • R-Value Free: 0.172 
  • R-Value Work: 0.149 
  • R-Value Observed: 0.150 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 44.89α = 113.02
b = 45.82β = 89.21
c = 48.52γ = 91.18
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
XSCALEdata scaling
Arcimboldophasing
ARP/wARPmodel building

Structure Validation

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Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
German Research FoundationGermanyDFG NI 643/4-2

Revision History  (Full details and data files)

  • Version 1.0: 2019-03-27
    Type: Initial release
  • Version 1.1: 2019-10-09
    Changes: Data collection, Database references
  • Version 1.2: 2024-05-15
    Changes: Data collection, Database references