4QZS

Crystal structure of the first bromodomain of human 3-fluoro tyrosine-labeled brd4 in complex with jq1

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.45 Å
  • R-Value Free: 0.185 
  • R-Value Work: 0.140 

Starting Model: experimental
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This is version 1.2 of the entry. See complete history. 


Literature

Fluorinated aromatic amino acids are sensitive (19)f NMR probes for bromodomain-ligand interactions.

Mishra, N.K., Urick, A.K., Ember, S.W., Schonbrunn, E., Pomerantz, W.C.

(2014) ACS Chem Biol 9: 2755-2760

  • DOI: https://doi.org/10.1021/cb5007344
  • Primary Citation of Related Structures:  
    4QZS

  • PubMed Abstract: 

    We describe a (19)F NMR method for detecting bromodomain-ligand interactions using fluorine-labeled aromatic amino acids due to the conservation of aromatic residues in the bromodomain binding site. We test the sensitivity, accuracy, and speed of this method with small molecule ligands (+)-JQ1, BI2536, Dinaciclib, TG101348, and acetaminophen using three bromodomains Brd4, BrdT, and BPTF. Simplified (19)F NMR spectra allowed for simultaneous testing of multiple bromodomains to assess selectivity and identification of a new BPTF ligand. Fluorine labeling only modestly affected the Brd4 structure and function assessed by isothermal titration calorimetry, circular dichroism, and X-ray crystallography. The speed, ease of interpretation, and low concentration of protein needed for binding experiments affords a new method to discover and characterize both native and new ligands.

    • Organizational Affiliation: 

    Department of Chemistry, University of Minnesota , 207 Pleasant St. SE, Minneapolis, Minnesota 55455, United States.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Bromodomain-containing protein 4127Homo sapiensMutation(s): 0 
Gene Names: BRD4, HUNK1
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
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
YOF
Query on YOF
A
L-PEPTIDE LINKINGC9 H10 F N O3TYR
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.45 Å
  • R-Value Free: 0.185 
  • R-Value Work: 0.140 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 36.767α = 90
b = 44.898β = 90
c = 78.597γ = 90
Software Package:
Software NamePurpose
SERGUIdata collection
PHASERphasing
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-10-29
    Type: Initial release
  • Version 1.1: 2015-01-21
    Changes: Database references
  • Version 1.2: 2023-09-20
    Changes: Data collection, Database references, Derived calculations, Refinement description