5MMR

Crystal Structure of CK2alpha with N-((2-chloro-[1,1'-biphenyl]-4-yl)methyl)butane-1,4-diamine bound


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.226 
  • R-Value Work: 0.196 
  • R-Value Observed: 0.197 

Starting Model: experimental
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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

A fragment-based approach leading to the discovery of a novel binding site and the selective CK2 inhibitor CAM4066.

De Fusco, C.Brear, P.Iegre, J.Georgiou, K.H.Sore, H.F.Hyvonen, M.Spring, D.R.

(2017) Bioorg Med Chem 25: 3471-3482

  • DOI: https://doi.org/10.1016/j.bmc.2017.04.037
  • Primary Citation of Related Structures:  
    5CT0, 5CTP, 5CU0, 5CU2, 5CX9, 5MMF, 5MMR, 5MO5, 5MO6, 5MO7, 5MO8, 5MOD, 5MOE, 5MOH, 5MOT, 5MOV, 5MOW, 5MP8, 5MPJ

  • PubMed Abstract: 

    Recently we reported the discovery of a potent and selective CK2α inhibitor CAM4066. This compound inhibits CK2 activity by exploiting a pocket located outside the ATP binding site (αD pocket). Here we describe in detail the journey that led to the discovery of CAM4066 using the challenging fragment linking strategy. Specifically, we aimed to develop inhibitors by linking a high-affinity fragment anchored in the αD site to a weakly binding warhead fragment occupying the ATP site. Moreover, we describe the remarkable impact that molecular modelling had on the development of this novel chemical tool. The work described herein shows potential for the development of a novel class of CK2 inhibitors.


  • Organizational Affiliation

    Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.


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
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  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
H83
Query on H83

Download Ideal Coordinates CCD File 
C [auth A],
D [auth A],
I [auth B]
~{N}'-[(3-chloranyl-4-phenyl-phenyl)methyl]butane-1,4-diamine
C17 H21 Cl N2
HJEYOGWGGOUBGH-UHFFFAOYSA-N
PO4
Query on PO4

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

Download Ideal Coordinates CCD File 
E [auth A],
F [auth A],
G [auth A],
H [auth A]
ACETATE ION
C2 H3 O2
QTBSBXVTEAMEQO-UHFFFAOYSA-M
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.226 
  • R-Value Work: 0.196 
  • R-Value Observed: 0.197 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 64.362α = 90
b = 67.715β = 90
c = 334.765γ = 90
Software Package:
Software NamePurpose
Aimlessdata scaling
PHASERphasing
BUSTERrefinement
PDB_EXTRACTdata extraction
autoPROCdata collection
XDSdata reduction
PHASERphasing
autoPROCdata reduction
CCP4data scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


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

Revision History  (Full details and data files)

  • Version 1.0: 2017-05-24
    Type: Initial release
  • Version 1.1: 2017-06-07
    Changes: Data collection, Database references
  • Version 1.2: 2024-01-17
    Changes: Data collection, Database references, Refinement description