RCSB PDB - 7ZAQ: BRD4 in complex with FragLite19

 7ZAQ

BRD4 in complex with FragLite19


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.11 Å
  • R-Value Free: 0.214 
  • R-Value Work: 0.193 

Starting Model: experimental
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wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted 3Z7Click on this verticalbar to view details

This is version 1.3 of the entry. See complete history


Literature

Mapping Ligand Interactions of Bromodomains BRD4 and ATAD2 with FragLites and PepLites─Halogenated Probes of Druglike and Peptide-like Molecular Interactions.

Davison, G.Martin, M.P.Turberville, S.Dormen, S.Heath, R.Heptinstall, A.B.Lawson, M.Miller, D.C.Ng, Y.M.Sanderson, J.N.Hope, I.Wood, D.J.Cano, C.Endicott, J.A.Hardcastle, I.R.Noble, M.E.M.Waring, M.J.

(2022) J Med Chem 65: 15416-15432

  • DOI: https://doi.org/10.1021/acs.jmedchem.2c01357
  • Primary Citation of Related Structures:  
    7PPX, 7QU7, 7QUK, 7QUM, 7QWO, 7QX1, 7QXT, 7QYK, 7QYL, 7QZM, 7QZY, 7QZZ, 7R00, 7R05, 7R0Y, 7Z9H, 7Z9I, 7Z9J, 7Z9N, 7Z9O, 7Z9S, 7Z9U, 7Z9W, 7Z9Y, 7ZA6, 7ZA7, 7ZA8, 7ZA9, 7ZAA, 7ZAD, 7ZAE, 7ZAJ, 7ZAQ, 7ZAR, 7ZAT, 7ZE6, 7ZE7, 7ZEF, 7ZEN, 7ZFN, 7ZFO, 7ZFS, 7ZFT, 7ZFU, 7ZFV, 7ZFY, 7ZFZ, 7ZG1, 7ZG2

  • PubMed Abstract: 

    The development of ligands for biological targets is critically dependent on the identification of sites on proteins that bind molecules with high affinity. A set of compounds, called FragLites, can identify such sites, along with the interactions required to gain affinity, by X-ray crystallography. We demonstrate the utility of FragLites in mapping the binding sites of bromodomain proteins BRD4 and ATAD2 and demonstrate that FragLite mapping is comparable to a full fragment screen in identifying ligand binding sites and key interactions. We extend the FragLite set with analogous compounds derived from amino acids (termed PepLites) that mimic the interactions of peptides. The output of the FragLite maps is shown to enable the development of ligands with leadlike potency. This work establishes the use of FragLite and PepLite screening at an early stage in ligand discovery allowing the rapid assessment of tractability of protein targets and informing downstream hit-finding.


  • Organizational Affiliation

    Cancer Research Horizons Therapeutic Innovation, Newcastle Drug Discovery Unit, Newcastle University Centre for Cancer, Chemistry, School of Natural and Environmental Sciences, Newcastle University, Bedson Building, Newcastle upon Tyne NE1 7RU, U.K.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Isoform C of Bromodomain-containing protein 4129Homo 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
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.11 Å
  • R-Value Free: 0.214 
  • R-Value Work: 0.193 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 37.732α = 90
b = 43.555β = 90
c = 79.628γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
REFMACrefinement
Aimlessdata scaling
xia2data reduction
PHASERphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted 3Z7Click on this verticalbar to view details

Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Cancer Research UKUnited KingdomC57659/A27310
Cancer Research UKUnited KingdomC1362/A20263
Cancer Research UKUnited KingdomC2215/A21421

Revision History  (Full details and data files)

  • Version 1.0: 2022-11-23
    Type: Initial release
  • Version 1.1: 2022-12-07
    Changes: Database references
  • Version 1.2: 2023-01-11
    Changes: Database references
  • Version 1.3: 2024-01-31
    Changes: Data collection, Refinement description