5IBN

Ultra high resolution crystal structure of the apo- form of second bromodomain of BRD2.


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 0.94 Å
  • R-Value Free: 0.145 
  • R-Value Work: 0.128 
  • R-Value Observed: 0.129 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

A Novel Phenanthridionone Based Scaffold As a Potential Inhibitor of the BRD2 Bromodomain: Crystal Structure of the Complex

Tripathi, S.Mathur, S.Deshmukh, P.Manjula, R.Padmanabhan, B.

(2016) PLoS One 11: e0156344-e0156344

  • DOI: https://doi.org/10.1371/journal.pone.0156344
  • Primary Citation of Related Structures:  
    5IBN, 5IG6

  • PubMed Abstract: 

    Bromodomain containing proteins recognize the level of histone acetylation and regulate epigenetically controlled processes like gene transcription and chromatin modification. The BET (bromodomain and extra-terminal) family proteins, which are transcriptional co-regulators, have been implicated in the pathogenesis of cancer, neurodegenerative disorders, and defects in embryonic stem cell differentiation. Inhibitors selectively targeting the BET bromodomains can pave the path for new drug discovery against several forms of major diseases. By a rational structure-based approach, we have identified a new inhibitor (NSC127133) of the second bromodomain (BD2) of the BET family protein BRD2 using the NCI Diversity Set III library. A high-resolution crystal structure of the BRD2-BD2 in complex with this compound and in apo- form is refined to 0.91 and 0.94 Å, respectively. The compound, which is a phenanthridinone derivative, binds well to the acetyl-lysine binding pocket of BD2 and displays significant hydrophobic and hydrophilic interactions. Moreover, the atomic resolution data obtained in this study allowed us to visualize certain structural features of BD2 which remained unobserved so far. We propose that the discovered compound may be a potential molecule to develop a new library for inhibiting the BRD2-BD2 function.


  • Organizational Affiliation

    Department of Biophysics, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bangalore, 560029, India.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Bromodomain-containing protein 2111Homo sapiensMutation(s): 0 
Gene Names: BRD2KIAA9001RING3
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
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  • Reference Sequence
Small Molecules
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 0.94 Å
  • R-Value Free: 0.145 
  • R-Value Work: 0.128 
  • R-Value Observed: 0.129 
  • Space Group: P 2 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 32.08α = 90
b = 52.46β = 90
c = 71.37γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
SCALAdata scaling
PDB_EXTRACTdata extraction
MOSFLMdata reduction
Phaser_MRphasing

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
DBTIndia--

Revision History  (Full details and data files)

  • Version 1.0: 2016-06-22
    Type: Initial release
  • Version 1.1: 2023-11-08
    Changes: Data collection, Database references, Derived calculations, Refinement description