4CFL

N-TERMINAL BROMODOMAIN OF HUMAN BRD4 WITH LY303511


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.32 Å
  • R-Value Free: 0.217 
  • R-Value Work: 0.189 
  • R-Value Observed: 0.191 

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Ligand Structure Quality Assessment 


This is version 1.2 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
Find similar proteins by:  (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
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
8DQ Binding MOAD:  4CFL Kd: 1330 (nM) from 1 assay(s)
BindingDB:  4CFL IC50: 9050 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.32 Å
  • R-Value Free: 0.217 
  • R-Value Work: 0.189 
  • R-Value Observed: 0.191 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 37.52α = 90
b = 44.48β = 90
c = 77.72γ = 90
Software Package:
Software NamePurpose
REFMACrefinement

Structure Validation

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Ligand Structure Quality Assessment 


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