5G4R

BROMODOMAIN OF HUMAN BRPF1 WITH N-1,3-dimethyl-6-2R-2- methylpiperazin-1-yl-2-oxo-2,3-dihydro-1H-1,3-benzodiazol-5-yl-2- methoxybenzamide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.96 Å
  • R-Value Free: 0.240 
  • R-Value Work: 0.200 
  • R-Value Observed: 0.202 

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Ligand Structure Quality Assessment 


This is version 1.0 of the entry. See complete history


Literature

Gsk6853, a Chemical Probe for Inhibition of the Brpf1 Bromodomain.

Bamborough, P.Barnett, H.A.Becher, I.Bird, M.J.Chung, C.Craggs, P.D.Demont, E.H.Diallo, H.Fallon, D.J.Gordon, L.J.Grandi, P.Hobbs, C.I.Hooper-Greenhill, E.Jones, E.J.Law, R.P.Le Gall, A.Lugo, D.Michon, A.Mitchell, D.J.Prinjha, R.K.Sheppard, R.J.Watson, A.J.B.Watson, R.J.

(2016) ACS Med Chem Lett 7: 552

  • DOI: https://doi.org/10.1021/acsmedchemlett.6b00092
  • Primary Citation of Related Structures:  
    5G4R, 5G4S

  • PubMed Abstract: 

    The BRPF (Bromodomain and PHD Finger-containing) protein family are important scaffolding proteins for assembly of MYST histone acetyltransferase complexes. A selective benzimidazolone BRPF1 inhibitor showing micromolar activity in a cellular target engagement assay was recently described. Herein, we report the optimization of this series leading to the identification of a superior BRPF1 inhibitor suitable for in vivo studies.


  • Organizational Affiliation

    Epinova Discovery Performance Unit, Quantitative Pharmacology, Experimental Medicine Unit, Flexible Discovery Unit, and Platform Technology and Science, GlaxoSmithKline , Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, U.K.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
PEREGRIN
A, B, C, D
118Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P55201 (Homo sapiens)
Explore P55201 
Go to UniProtKB:  P55201
PHAROS:  P55201
GTEx:  ENSG00000156983 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP55201
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
LF1 BindingDB:  5G4R Kd: 0.32 (nM) from 1 assay(s)
IC50: min: 2.5, max: 20 (nM) from 3 assay(s)
Binding MOAD:  5G4R IC50: 7.94 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.96 Å
  • R-Value Free: 0.240 
  • R-Value Work: 0.200 
  • R-Value Observed: 0.202 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 47.444α = 72.61
b = 50.703β = 71.36
c = 61.981γ = 66.64
Software Package:
Software NamePurpose
REFMACrefinement
XDSdata reduction
SCALAdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

  • Released Date: 2016-07-06 
  • Deposition Author(s): Chung, C.

Revision History  (Full details and data files)

  • Version 1.0: 2016-07-06
    Type: Initial release