4ALG

N-Terminal Bromodomain of Human BRD2 With IBET-151

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.60 Å
  • R-Value Free: 0.202 
  • R-Value Work: 0.176 
  • R-Value Observed: 0.177 

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Ligand Structure Quality Assessment 


This is version 1.1 of the entry. See complete history. 


Literature

Identification of a Novel Series of Bet Family Bromodomain Inhibitors: Binding Mode and Profile of I-Bet151 (Gsk1210151A).

Seal, J., Lamotte, Y., Donche, F., Bouillot, A., Mirguet, O., Gellibert, F., Nicodeme, E., Krysa, G., Kirilovsky, J., Beinke, S., Mccleary, S., Rioja, I., Bamborough, P., Chung, C., Gordon, L., Lewis, T., Walker, A.L., Cutler, L., Lugo, D., Wilson, D.M., Witherington, J., Lee, K., Prinjha, R.K.

(2012) Bioorg Med Chem Lett 22: 2968

  • DOI: https://doi.org/10.1016/j.bmcl.2012.02.041
  • Primary Citation of Related Structures:  
    4AKN, 4ALG

  • PubMed Abstract: 

    A novel series of quinoline isoxazole BET family bromodomain inhibitors are discussed. Crystallography is used to illustrate binding modes and rationalize their SAR. One member, I-BET151 (GSK1210151A), shows good oral bioavailability in both the rat and minipig as well as demonstrating efficient suppression of bacterial induced inflammation and sepsis in a murine in vivo endotoxaemia model.

    • Organizational Affiliation: 

    Epinova DPU, GlaxoSmithKline R&D, Medicines Research Centre, Stevenage, Hertfordshire, UK. jon.t.seal@gsk.com


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
BROMODOMAIN-CONTAINING PROTEIN 2154Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P25440 (Homo sapiens)
Explore P25440 
Go to UniProtKB:  P25440
PHAROS:  P25440
GTEx:  ENSG00000204256 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP25440
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
1GH
Query on 1GH
Download Ideal Coordinates CCD File 
D [auth A]7-(3,5-DIMETHYL-1,2-OXAZOL-4-YL)-8-METHOXY-1-[(1R)-1-(PYRIDIN-2-YL)ETHYL]-1H,2H,3H-IMIDAZO[4,5-C]QUINOLIN-2-ONE
C23 H21 N5 O3
VUVUVNZRUGEAHB-CYBMUJFWSA-N
GOL
Query on GOL
Download Ideal Coordinates CCD File 
C [auth A]GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
ACT
Query on ACT
Download Ideal Coordinates CCD File 
B [auth A]ACETATE ION
C2 H3 O2
QTBSBXVTEAMEQO-UHFFFAOYSA-M
Binding Affinity Annotations 
IDSourceBinding Affinity
1GH PDBBind:  4ALG IC50: 500 (nM) from 1 assay(s)
Binding MOAD:  4ALG IC50: 500 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.60 Å
  • R-Value Free: 0.202 
  • R-Value Work: 0.176 
  • R-Value Observed: 0.177 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 82.05α = 90
b = 40.303β = 113.22
c = 48.347γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-07-04
    Type: Initial release
  • Version 1.1: 2019-05-15
    Changes: Data collection, Experimental preparation, Other