6EII

The crystal structure of CK2alpha in complex with compound 18


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.94 Å
  • R-Value Free: 0.234 
  • R-Value Work: 0.208 
  • R-Value Observed: 0.209 

Starting Model: experimental
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wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Second-generation CK2 alpha inhibitors targeting the alpha D pocket.

Iegre, J.Brear, P.De Fusco, C.Yoshida, M.Mitchell, S.L.Rossmann, M.Carro, L.Sore, H.F.Hyvonen, M.Spring, D.R.

(2018) Chem Sci 9: 3041-3049

  • DOI: https://doi.org/10.1039/c7sc05122k
  • Primary Citation of Related Structures:  
    5OQU, 5ORH, 5ORJ, 5ORK, 5OS7, 5OS8, 5OSL, 5OSP, 5OSR, 5OSU, 5OSZ, 5OT5, 5OT6, 5OTD, 5OTH, 5OTI, 5OTL, 5OTO, 5OTP, 5OTQ, 5OTR, 5OTS, 5OTY, 5OTZ, 5OUE, 5OUL, 5OUM, 5OUU, 5OYF, 6EHK, 6EHU, 6EII

  • PubMed Abstract: 

    CK2 is a critical cell cycle regulator that also promotes various anti-apoptotic mechanisms. Development of ATP-non-competitive inhibitors of CK2 is a very attractive strategy considering that the ATP binding site is highly conserved among other kinases. We have previously utilised a pocket outside the active site to develop a novel CK2 inhibitor, CAM4066 . Whilst CAM4066 bound to this new pocket it was also interacting with the ATP site: herein, we describe an example of a CK2α inhibitor that binds completely outside the active site. This second generation αD-site binding inhibitor, compound CAM4712 (IC 50 = 7 μM, GI 50 = 10.0 ± 3.6 μM), has numerous advantages over the previously reported CAM4066 , including a reduction in the number of rotatable bonds, the absence of amide groups susceptible to the action of proteases and improved cellular permeability. Unlike with CAM4066 , there was no need to facilitate cellular uptake by making a prodrug. Moreover, CAM4712 displayed no drop off between its ability to inhibit the kinase in vitro (IC 50 ) and the ability to inhibit cell proliferation (GI 50 ).


  • Organizational Affiliation

    Department of Chemistry , University of Cambridge , CB2 1EW , Cambridge , UK . Email: [email protected].


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Casein kinase II subunit alpha
A, B
352Homo sapiensMutation(s): 1 
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
B5W (Subject of Investigation/LOI)
Query on B5W

Download Ideal Coordinates CCD File 
G [auth A],
L [auth B]
(3-chloranyl-4-phenyl-phenyl)methyl-(3-phenylpropyl)azanium
C22 H23 Cl N
IAHQDSBGJLCLQL-UHFFFAOYSA-O
PO4
Query on PO4

Download Ideal Coordinates CCD File 
E [auth A],
F [auth A],
J [auth B],
K [auth B]
PHOSPHATE ION
O4 P
NBIIXXVUZAFLBC-UHFFFAOYSA-K
ACT
Query on ACT

Download Ideal Coordinates CCD File 
C [auth A],
D [auth A],
H [auth B],
I [auth B]
ACETATE ION
C2 H3 O2
QTBSBXVTEAMEQO-UHFFFAOYSA-M
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.94 Å
  • R-Value Free: 0.234 
  • R-Value Work: 0.208 
  • R-Value Observed: 0.209 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 65.918α = 90
b = 66.226β = 90
c = 333.16γ = 90
Software Package:
Software NamePurpose
Aimlessdata scaling
BUSTERrefinement
PDB_EXTRACTdata extraction
XDSdata reduction
PHASERphasing
XDSdata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Wellcome TrustUnited Kingdom090340/Z/09/Z
Wellcome TrustUnited Kingdom107714/Z/15/Z

Revision History  (Full details and data files)

  • Version 1.0: 2018-02-28
    Type: Initial release
  • Version 1.1: 2018-05-16
    Changes: Data collection, Database references
  • Version 1.2: 2019-10-09
    Changes: Data collection, Derived calculations
  • Version 1.3: 2024-01-17
    Changes: Data collection, Database references, Refinement description