6HBN

HIGH-SALT STRUCTURE OF PROTEIN KINASE CK2 CATALYTIC SUBUNIT (ISOFORM CK2ALPHA/CSKN2A1 GENE PRODUCT) IN COMPLEX WITH THE INDENOINDOLE-TYPE INHIBITOR THN27


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.59 Å
  • R-Value Free: 0.217 
  • R-Value Work: 0.187 
  • R-Value Observed: 0.188 

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Ligand Structure Quality Assessment 


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
A, B
335Homo sapiensMutation(s): 0 
Gene Names: CSNK2A1CK2A1
EC: 2.7.11.1
UniProt & NIH Common Fund Data Resources
Find proteins for P68400 (Homo sapiens)
Explore P68400 
Go to UniProtKB:  P68400
PHAROS:  P68400
GTEx:  ENSG00000101266 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP68400
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
FXB
Query on FXB

Download Ideal Coordinates CCD File 
H [auth A],
O [auth B]
5-propan-2-yl-4-prop-2-enoxy-7,8-dihydro-6~{H}-indeno[1,2-b]indole-9,10-dione
C21 H21 N O3
SPPQIWGQWJYZTO-UHFFFAOYSA-N
CL
Query on CL

Download Ideal Coordinates CCD File 
C [auth A]
D [auth A]
E [auth A]
F [auth A]
G [auth A]
C [auth A],
D [auth A],
E [auth A],
F [auth A],
G [auth A],
J [auth B],
K [auth B],
L [auth B],
M [auth B],
N [auth B]
CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
NA
Query on NA

Download Ideal Coordinates CCD File 
I [auth A],
P [auth B],
Q [auth B]
SODIUM ION
Na
FKNQFGJONOIPTF-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.59 Å
  • R-Value Free: 0.217 
  • R-Value Work: 0.187 
  • R-Value Observed: 0.188 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 71.55α = 90
b = 71.62β = 90
c = 128.03γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
XSCALEdata scaling
PHASERphasing

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: 2024-01-17
    Changes: Data collection, Database references, Derived calculations, Refinement description