3I3J

Crystal Structure of the Bromodomain of Human EP300


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.33 Å
  • R-Value Free: 0.275 
  • R-Value Work: 0.229 
  • R-Value Observed: 0.231 

wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

Histone recognition and large-scale structural analysis of the human bromodomain family.

Filippakopoulos, P.Picaud, S.Mangos, M.Keates, T.Lambert, J.P.Barsyte-Lovejoy, D.Felletar, I.Volkmer, R.Muller, S.Pawson, T.Gingras, A.C.Arrowsmith, C.H.Knapp, S.

(2012) Cell 149: 214-231

  • DOI: https://doi.org/10.1016/j.cell.2012.02.013
  • Primary Citation of Related Structures:  
    2NXB, 2OO1, 2OSS, 2OUO, 2RFJ, 3D7C, 3DAI, 3DWY, 3GG3, 3HME, 3HMF, 3HMH, 3I3J, 3IU5, 3IU6, 3LXJ, 3MB3, 3MB4, 3MQM, 3NXB, 3P1C, 3P1D, 3Q2E, 3RCW, 3TLP, 3UV2, 3UV4, 3UV5, 3UVD, 3UVW, 3UVX, 3UVY, 3UW9

  • PubMed Abstract: 

    Bromodomains (BRDs) are protein interaction modules that specifically recognize ε-N-lysine acetylation motifs, a key event in the reading process of epigenetic marks. The 61 BRDs in the human genome cluster into eight families based on structure/sequence similarity. Here, we present 29 high-resolution crystal structures, covering all BRD families. Comprehensive crossfamily structural analysis identifies conserved and family-specific structural features that are necessary for specific acetylation-dependent substrate recognition. Screening of more than 30 representative BRDs against systematic histone-peptide arrays identifies new BRD substrates and reveals a strong influence of flanking posttranslational modifications, such as acetylation and phosphorylation, suggesting that BRDs recognize combinations of marks rather than singly acetylated sequences. We further uncovered a structural mechanism for the simultaneous binding and recognition of diverse diacetyl-containing peptides by BRD4. These data provide a foundation for structure-based drug design of specific inhibitors for this emerging target family.


  • Organizational Affiliation

    Nuffield Department of Clinical Medicine, Structural Genomics Consortium, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7LD, UK. panagis.filippakopoulos@sgc.ox.ac.uk


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Histone acetyltransferase p300
A, B, C, D, E
A, B, C, D, E, F, G, H, I, J, K, L
124Homo sapiensMutation(s): 0 
Gene Names: EP300P300
EC: 2.3.1.48
UniProt & NIH Common Fund Data Resources
Find proteins for Q09472 (Homo sapiens)
Explore Q09472 
Go to UniProtKB:  Q09472
PHAROS:  Q09472
GTEx:  ENSG00000100393 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ09472
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.33 Å
  • R-Value Free: 0.275 
  • R-Value Work: 0.229 
  • R-Value Observed: 0.231 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 64.899α = 90
b = 86.186β = 96.98
c = 149.897γ = 90
Software Package:
Software NamePurpose
SCALAdata scaling
PHASERphasing
PHENIXrefinement
PDB_EXTRACTdata extraction
CrystalCleardata collection
MOSFLMdata reduction

Structure Validation

View Full Validation Report



Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2009-07-28
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2012-03-14
    Changes: Other
  • Version 1.3: 2012-04-11
    Changes: Database references
  • Version 1.4: 2013-05-08
    Changes: Other
  • Version 1.5: 2023-11-01
    Changes: Data collection, Database references, Derived calculations, Refinement description