5LJ0

Crystal structure of human ATAD2 bromodomain in complex with 8-(((3R,4R,5S)-3-((4,4-difluorocyclohexyl)methoxy)-5-methoxypiperidin-4-yl)amino)-3-methyl-5-(5-methylpyridin-3-yl)-1,7-naphthyridin-2(1H)-one

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.82 Å
  • R-Value Free: 0.183 
  • R-Value Work: 0.174 
  • R-Value Observed: 0.174 

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Literature

A Chemical Probe for the ATAD2 Bromodomain.

Bamborough, P., Chung, C.W., Demont, E.H., Furze, R.C., Bannister, A.J., Che, K.H., Diallo, H., Douault, C., Grandi, P., Kouzarides, T., Michon, A.M., Mitchell, D.J., Prinjha, R.K., Rau, C., Robson, S., Sheppard, R.J., Upton, R., Watson, R.J.

(2016) Angew Chem Int Ed Engl 55: 11382-11386

  • DOI: https://doi.org/10.1002/anie.201603928
  • Primary Citation of Related Structures:  
    5LJ0, 5LJ1, 5LJ2

  • PubMed Abstract: 

    ATAD2 is a cancer-associated protein whose bromodomain has been described as among the least druggable of that target class. Starting from a potent lead, permeability and selectivity were improved through a dual approach: 1) using CF2 as a sulfone bio-isostere to exploit the unique properties of fluorine, and 2) using 1,3-interactions to control the conformation of a piperidine ring. This resulted in the first reported low-nanomolar, selective and cell permeable chemical probe for ATAD2.

    • Organizational Affiliation: 

    GlaxoSmithKline, Gunnels Wood Road, Stevenage, SG1 2NY, UK. Paul.A.Bamborough@gsk.com.


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
ATPase family AAA domain-containing protein 2130Homo sapiensMutation(s): 0 
Gene Names: ATAD2, L16, PRO2000
EC: 3.6.1.3
UniProt & NIH Common Fund Data Resources
Find proteins for Q6PL18 (Homo sapiens)
Explore Q6PL18 
Go to UniProtKB:  Q6PL18
PHAROS:  Q6PL18
GTEx:  ENSG00000156802 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ6PL18
Sequence Annotations
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  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
6XX BindingDB:  5LJ0 IC50: 50 (nM) from 1 assay(s)
Binding MOAD:  5LJ0 IC50: 10 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.82 Å
  • R-Value Free: 0.183 
  • R-Value Work: 0.174 
  • R-Value Observed: 0.174 
  • Space Group: P 65 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 79.158α = 90
b = 79.158β = 90
c = 135.857γ = 120
Software Package:
Software NamePurpose
REFMACrefinement
XDSdata reduction
SCALAdata scaling

Structure Validation

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Entry History 

Deposition Data

  • Released Date: 2016-08-31 
    • Deposition Author(s): Chung, C.

Revision History  (Full details and data files)

  • Version 1.0: 2016-08-31
    Type: Initial release
  • Version 1.1: 2016-09-14
    Changes: Database references