6Q38

The Crystal structure of CK2a bound to P1-C4


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.74 Å
  • R-Value Free: 0.234 
  • R-Value Work: 0.204 
  • R-Value Observed: 0.205 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 2.0 of the entry. See complete history


Literature

Efficient development of stable and highly functionalised peptides targeting the CK2 alpha /CK2 beta protein-protein interaction.

Iegre, J.Brear, P.Baker, D.J.Tan, Y.S.Atkinson, E.L.Sore, H.F.O' Donovan, D.H.Verma, C.S.Hyvonen, M.Spring, D.R.

(2019) Chem Sci 10: 5056-5063

  • DOI: https://doi.org/10.1039/c9sc00798a
  • Primary Citation of Related Structures:  
    6Q38, 6Q4Q

  • PubMed Abstract: 

    The discovery of new Protein-Protein Interaction (PPI) modulators is currently limited by the difficulties associated with the design and synthesis of selective small molecule inhibitors. Peptides are a potential solution for disrupting PPIs; however, they typically suffer from poor stability in vivo and limited tissue penetration hampering their wide spread use as new chemical biology tools and potential therapeutics. In this work, a combination of CuAAC chemistry, molecular modelling, X-ray crystallography, and biological validation allowed us to develop highly functionalised peptide PPI inhibitors of the protein CK2. The lead peptide, CAM7117 , prevents the formation of the holoenzyme assembly in vitro , slows down proliferation, induces apoptosis in cancer cells and is stable in human serum. CAM7117 could aid the development of novel CK2 inhibitors acting at the interface and help to fully understand the intracellular pathways involving CK2. Importantly, the approach adopted herein could be applied to many PPI targets and has the potential to ease the study of PPIs by efficiently providing access to functionalised peptides.


  • Organizational Affiliation

    Department of Chemistry , University of Cambridge , Lensfield Road , CB2 1EW , Cambridge , UK . Email: spring@ch.cam.ac.uk.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Casein kinase II subunit alpha327Homo 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

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Stapled Peptide15Homo sapiensMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
A1H27
Query on A1H27

Download Ideal Coordinates CCD File 
D [auth B]3,5-bis(1-methyl-1,2,3-triazol-4-yl)benzoic acid
C13 H12 N6 O2
PDMVDNGDJJRIED-UHFFFAOYSA-N
BEZ
Query on BEZ

Download Ideal Coordinates CCD File 
C [auth A]BENZOIC ACID
C7 H6 O2
WPYMKLBDIGXBTP-UHFFFAOYSA-N
Biologically Interesting Molecules (External Reference) 1 Unique
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.74 Å
  • R-Value Free: 0.234 
  • R-Value Work: 0.204 
  • R-Value Observed: 0.205 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 60.887α = 90
b = 127.752β = 90
c = 54.499γ = 90
Software Package:
Software NamePurpose
BUSTERrefinement
Aimlessdata scaling
PHASERphasing
PDB_EXTRACTdata extraction
XDSdata reduction

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
Wellcome TrustUnited Kingdom107714/Z/15/Z

Revision History  (Full details and data files)

  • Version 1.0: 2019-04-24
    Type: Initial release
  • Version 1.1: 2019-06-19
    Changes: Data collection, Database references
  • Version 1.2: 2024-01-24
    Changes: Data collection, Database references, Derived calculations, Refinement description
  • Version 2.0: 2024-03-06
    Changes: Atomic model, Data collection, Database references, Derived calculations, Non-polymer description, Other, Polymer sequence, Refinement description, Source and taxonomy, Structure summary