9HL0 | pdb_00009hl0

Protein Kinase CK2 and small molecule ligands


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.63 Å
  • R-Value Free: 
    0.280 (Depositor), 0.274 (DCC) 
  • R-Value Work: 
    0.230 (Depositor), 0.229 (DCC) 
  • R-Value Observed: 
    0.233 (Depositor) 

Starting Model: experimental
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Ligand Structure Quality Assessment 


This is version 1.0 of the entry. See complete history


Literature

Binding-Site Switch for Protein Kinase CK2 Inhibitors.

Grenier, D.Gelin, M.Yang, Y.Mularoni, A.Guichou, J.F.Delcros, J.G.Krimm, I.

(2025) ChemMedChem 20: e202400868-e202400868

  • DOI: https://doi.org/10.1002/cmdc.202400868
  • Primary Citation of Related Structures:  
    9HKP, 9HKS, 9HL0, 9HL7

  • PubMed Abstract: 

    The serine/threonine protein kinase CK2, a tetramer composed of a regulatory dimer (CK2β 2 ) bound to two catalytic subunits CK2α, is a well-established therapeutic target for various pathologies, including cancer and viral infections. Several types of CK2 inhibitors have been developed, including inhibitors that bind to the catalytic ATP-site, bivalent inhibitors that occupy both the CK2α ATP-site and the αD pocket, and inhibitors that target the CK2α/CK2β interface. Interestingly, the bivalent inhibitor AB668 shares a similar chemical structure with the interface inhibitor CCH507. In this study, we designed analogs of CCH507 using structure-based and fragment-based approaches. The ability of these analogs to bind the CK2α/CK2β interface was evaluated using biolayer interferometry and fluorescence anisotropy-based assays. Their potency to inhibit CK2 kinase activity was determined using the bioluminescent ADP-Glo assay. These experiments allowed us to investigate which chemical modifications prevent the binding of the compounds at the CK2α/CK2β interface. Seven out of sixteen compounds conserved the ability to bind at the protein-protein interface, among which three compounds exhibited better interface inhibition compared to CCH507.


  • Organizational Affiliation
    • Univ Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de recherche en cancérologie de Lyon, Lyon, 69373, France.

Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Casein kinase II subunit alpha
A, B
359Homo 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
A1IVS (Subject of Investigation/LOI)
Query on A1IVS

Download Ideal Coordinates CCD File 
H [auth A],
O [auth B],
R [auth B]
5,7-bis(fluoranyl)-1~{H}-indole
C8 H5 F2 N
WZPOGQRJXZGSMH-UHFFFAOYSA-N
PEG
Query on PEG

Download Ideal Coordinates CCD File 
G [auth A],
L [auth B]
DI(HYDROXYETHYL)ETHER
C4 H10 O3
MTHSVFCYNBDYFN-UHFFFAOYSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
C [auth A]
D [auth A]
E [auth A]
F [auth A]
I [auth A]
C [auth A],
D [auth A],
E [auth A],
F [auth A],
I [auth A],
J [auth A],
K [auth A],
M [auth B],
N [auth B],
P [auth B],
Q [auth B]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.63 Å
  • R-Value Free:  0.280 (Depositor), 0.274 (DCC) 
  • R-Value Work:  0.230 (Depositor), 0.229 (DCC) 
  • R-Value Observed: 0.233 (Depositor) 
Space Group: P 43 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 127.3α = 90
b = 127.3β = 90
c = 123.958γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
XDSdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Agence Nationale de la Recherche (ANR)FranceANR-17-CONV-002
Agence Nationale de la Recherche (ANR)FranceANR-21-CE18-0014-01

Revision History  (Full details and data files)

  • Version 1.0: 2025-07-30
    Type: Initial release