5EI4

First domain of human bromodomain BRD4 in complex with inhibitor 8-(5-Amino-1H-[1,2,4]triazol-3-ylsulfanylmethyl)-3-(4-chlorobenzyl)-7-ethyl-3,7-dihydropurine-2,6-dione


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.05 Å
  • R-Value Free: 0.192 
  • R-Value Work: 0.171 
  • R-Value Observed: 0.172 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Exploring Selective Inhibition of the First Bromodomain of the Human Bromodomain and Extra-terminal Domain (BET) Proteins.

Raux, B.Voitovich, Y.Derviaux, C.Lugari, A.Rebuffet, E.Milhas, S.Priet, S.Roux, T.Trinquet, E.Guillemot, J.C.Knapp, S.Brunel, J.M.Fedorov, A.Y.Collette, Y.Roche, P.Betzi, S.Combes, S.Morelli, X.

(2016) J Med Chem 59: 1634-1641

  • DOI: https://doi.org/10.1021/acs.jmedchem.5b01708
  • Primary Citation of Related Structures:  
    5EGU, 5EI4, 5EIS

  • PubMed Abstract: 

    A midthroughput screening follow-up program targeting the first bromodomain of the human BRD4 protein, BRD4(BD1), identified an acetylated-mimic xanthine derivative inhibitor. This compound binds with an affinity in the low micromolar range yet exerts suitable unexpected selectivity in vitro against the other members of the bromodomain and extra-terminal domain (BET) family. A structure-based program pinpointed a role of the ZA loop, paving the way for the development of potent and selective BET-BRDi probes.


  • Organizational Affiliation

    Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Marseille (CRCM), UMR 7258; INSERM U1068; Institut Paoli-Calmettes; Aix-Marseille Université, UM105 , 13273 Marseille, France.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Bromodomain-containing protein 4127Homo sapiensMutation(s): 0 
Gene Names: BRD4HUNK1
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
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
5NV
Query on 5NV

Download Ideal Coordinates CCD File 
C [auth A]8-[(3-azanyl-1~{H}-1,2,4-triazol-5-yl)sulfanylmethyl]-3-[(4-chlorophenyl)methyl]-7-ethyl-purine-2,6-dione
C17 H17 Cl N8 O2 S
HZXIXZPCCYPTDC-UHFFFAOYSA-N
EDO
Query on EDO

Download Ideal Coordinates CCD File 
B [auth A]1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
5NV Binding MOAD:  5EI4 IC50: 2.64e+4 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.05 Å
  • R-Value Free: 0.192 
  • R-Value Work: 0.171 
  • R-Value Observed: 0.172 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 37.353α = 90
b = 44.069β = 90
c = 78.272γ = 90
Software Package:
Software NamePurpose
XDSdata reduction
PHASERphasing
REFMACrefinement
XDSdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2016-01-20
    Type: Initial release
  • Version 1.1: 2016-03-09
    Changes: Database references
  • Version 1.2: 2024-01-10
    Changes: Data collection, Database references, Refinement description