4CFK

N-TERMINAL BROMODOMAIN OF HUMAN BRD4 WITH LY294002

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.55 Å
  • R-Value Free: 0.267 
  • R-Value Work: 0.230 
  • R-Value Observed: 0.232 

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This is version 1.4 of the entry. See complete history. 


Literature

The Commonly Used Pi3-Kinase Probe Ly294002 is an Inhibitor of Bet Bromodomains.

Dittmann, A., Werner, T., Chung, C., Savitski, M.M., Falth Savitski, M., Grandi, P., Hopf, C., Lindon, M., Neubauer, G., Prinjha, R.K., Bantscheff, M., Drewes, G.

(2014) ACS Chem Biol 9: 495

  • DOI: https://doi.org/10.1021/cb400789e
  • Primary Citation of Related Structures:  
    4CFK, 4CFL

  • PubMed Abstract: 

    A commonly used small-molecule probe in cell-signaling research is the phosphoinositide 3-kinase inhibitor LY294002. Quantitative chemoproteomic profiling shows that LY294002 and LY303511, a close analogue devoid of PI3K activity, inhibit the BET bromodomain proteins BRD2, BRD3, and BRD4 that comprise a family of targets structurally unrelated to PI3K. Both compounds competitively inhibit acetyl-lysine binding of the first but not the second bromodomain of BET proteins in cell extracts. X-ray crystallography shows that the chromen-4-one scaffold represents a new bromodomain pharmacophore and establishes LY294002 as a dual kinase and BET-bromodomain inhibitor, whereas LY303511 exhibits anti-inflammatory and antiproliferative effects similar to the recently discovered BET inhibitors.

    • Organizational Affiliation: 

    Cellzome GmbH , Meyerhofstrasse 1, 69117 Heidelberg, Germany.


Macromolecules
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(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
BRD4 PROTEIN127Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for O60885 (Homo sapiens)
Explore O60885 
Go to UniProtKB:  O60885
PHAROS:  O60885
GTEx:  ENSG00000141867 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO60885
Sequence Annotations
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  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
LY2 BindingDB:  4CFK IC50: min: 5330, max: 1.24e+4 (nM) from 2 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.55 Å
  • R-Value Free: 0.267 
  • R-Value Work: 0.230 
  • R-Value Observed: 0.232 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 37.45α = 90
b = 43.68β = 90
c = 78.51γ = 90
Software Package:
Software NamePurpose
REFMACrefinement

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-01-15
    Type: Initial release
  • Version 1.1: 2014-02-26
    Changes: Database references
  • Version 1.2: 2014-03-05
    Changes: Database references
  • Version 1.3: 2019-05-15
    Changes: Data collection, Experimental preparation, Other
  • Version 1.4: 2024-05-08
    Changes: Data collection, Database references, Derived calculations, Other