5HCL

Crystal Structure of the first bromodomain of BRD4 in complex with DMA


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.50 Å
  • R-Value Free: 0.175 
  • R-Value Work: 0.145 
  • R-Value Observed: 0.147 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

N,N Dimethylacetamide a drug excipient that acts as bromodomain ligand for osteoporosis treatment.

Ghayor, C.Gjoksi, B.Dong, J.Siegenthaler, B.Caflisch, A.Weber, F.E.

(2017) Sci Rep 7: 42108-42108

  • DOI: https://doi.org/10.1038/srep42108
  • Primary Citation of Related Structures:  
    5HCL

  • PubMed Abstract: 

    N,N-Dimethylacetamide (DMA) is a water-miscible solvent, FDA approved as excipient and therefore widely used as drug-delivery vehicle. As such, DMA should be devoid of any bioactivity. Here we report that DMA is epigenetically active since it binds bromodomains and inhibits osteoclastogenesis and inflammation. Moreover, DMA enhances bone regeneration in vivo. Therefore, our in vivo and in vitro data reveal DMA's potential as an anti-osteoporotic agent via the inhibition of osteoclast mediated bone resorption and enhanced bone regeneration. Our results highlight the potential therapeutic benefits of DMA and the need for reconsideration of previous reports where DMA was used as an 'inactive' drug-delivery vehicle.


  • Organizational Affiliation

    Oral Biotechnology &Bioengineering, Center for Dental Medicine/MKG, University of Zürich, Switzerland.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Bromodomain-containing protein 4127Homo 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
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
5Y9
Query on 5Y9

Download Ideal Coordinates CCD File 
B [auth A]~{N},~{N}-dimethylethanamide
C4 H9 N O
FXHOOIRPVKKKFG-UHFFFAOYSA-N
EDO
Query on EDO

Download Ideal Coordinates CCD File 
C [auth A]1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
5Y9 Binding MOAD:  5HCL IC50: 6.00e+6 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.50 Å
  • R-Value Free: 0.175 
  • R-Value Work: 0.145 
  • R-Value Observed: 0.147 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 37.615α = 90
b = 43.83β = 90
c = 78.459γ = 90
Software Package:
Software NamePurpose
SCALAdata scaling
PHASERphasing
PHENIXrefinement
PDB_EXTRACTdata extraction
XDSdata reduction
Cootmodel building

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2017-01-25
    Type: Initial release
  • Version 1.1: 2017-02-15
    Changes: Database references
  • Version 1.2: 2017-02-22
    Changes: Database references
  • Version 1.3: 2024-01-10
    Changes: Data collection, Database references, Refinement description