5LPM

Crystal structure of the bromodomain of human Ep300 bound to the inhibitor XDM3d


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.50 Å
  • R-Value Free: 0.187 
  • R-Value Work: 0.158 
  • R-Value Observed: 0.159 

Starting Model: other
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wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Beyond the BET Family: Targeting CBP/p300 with 4-Acyl Pyrroles.

Hugle, M.Lucas, X.Ostrovskyi, D.Regenass, P.Gerhardt, S.Einsle, O.Hau, M.Jung, M.Breit, B.Gunther, S.Wohlwend, D.

(2017) Angew Chem Int Ed Engl 56: 12476-12480

  • DOI: https://doi.org/10.1002/anie.201705516
  • Primary Citation of Related Structures:  
    5LPJ, 5LPK, 5LPL, 5LPM, 5NRW, 5NU3, 5NU5

  • PubMed Abstract: 

    Bromodomain and extra-terminal domain (BET) inhibitors are widely used both as chemical tools to study the biological role of their targets in living organisms and as candidates for drug development against several cancer variants and human disorders. However, non-BET bromodomains such as those in p300 and CBP are less studied. XDM-CBP is a highly potent and selective inhibitor for the bromodomains of CBP and p300 derived from a pan-selective BET BRD-binding fragment. Along with X-ray crystal-structure analysis and thermodynamic profiling, XDM-CBP was used in screenings of several cancer cell lines in vitro to study its inhibitory potential on cancer cell proliferation. XDM-CBP is demonstrated to be a potent and selective CBP/p300 inhibitor that acts on specific cancer cell lines, in particular malignant melanoma, breast cancer, and leukemia.


  • Organizational Affiliation

    Institut für Biochemie, Albert-Ludwigs-Universität Freiburg, Albertstrasse 21, 79104, Freiburg, Germany.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Histone acetyltransferase p300
A, B
116Homo sapiensMutation(s): 0 
Gene Names: EP300P300
EC: 2.3.1.48 (PDB Primary Data), 2.3.1 (UniProt)
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
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
71Y
Query on 71Y

Download Ideal Coordinates CCD File 
C [auth A],
D [auth A],
G [auth B],
H [auth B]
~{N}-[(1~{S},2~{S})-7-chloranyl-2-oxidanyl-1,2,3,4-tetrahydronaphthalen-1-yl]-4-ethanoyl-3-ethyl-5-methyl-1~{H}-pyrrole -2-carboxamide
C20 H23 Cl N2 O3
KVJAGYRUNZONPJ-WMZOPIPTSA-N
ACT
Query on ACT

Download Ideal Coordinates CCD File 
E [auth A],
F [auth A],
I [auth B]
ACETATE ION
C2 H3 O2
QTBSBXVTEAMEQO-UHFFFAOYSA-M
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.50 Å
  • R-Value Free: 0.187 
  • R-Value Work: 0.158 
  • R-Value Observed: 0.159 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 37.861α = 90
b = 81.087β = 110.58
c = 44.779γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
Aimlessdata scaling
PHASERphasing
PDB_EXTRACTdata extraction

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
German Research FoundationGermanyWO2012/1-1

Revision History  (Full details and data files)

  • Version 1.0: 2017-08-16
    Type: Initial release
  • Version 1.1: 2017-10-11
    Changes: Database references
  • Version 1.2: 2024-05-01
    Changes: Data collection, Database references, Derived calculations, Refinement description, Structure summary