› 4c67

X-ray diffraction
1.55Å resolution

Discovery of Epigenetic Regulator I-BET762: Lead Optimization to Afford a Clinical Candidate Inhibitor of the BET Bromodomains

Released:
DOI: 10.2210/pdb4c67/pdb
PDB entry 4c67 coloured by chain, front view.
PDB entry 4c67 coloured by chain, side view.
PDB entry 4c67 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of epigenetic regulator I-BET762: lead optimization to afford a clinical candidate inhibitor of the BET bromodomains.
Mirguet O, Gosmini R, Toum J, Clément CA, Barnathan M, Brusq JM, Mordaunt JE, Grimes RM, Crowe M, Pineau O, Ajakane M, Daugan A, Jeffrey P, Cutler L, Haynes AC, Smithers NN, Chung CW, Bamborough P, Uings IJ, Lewis A, Witherington J, Parr N, Prinjha RK, Nicodème E
J Med Chem 56 7501-15 (2013)
PMID: 24015967

Function and Biology Details

Biochemical function:
  • not assigned
Biological process:
  • not assigned
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-130112 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Bromodomain-containing protein 4 Chain: A
Molecule details ›
Chain: A
Length: 127 amino acids
Theoretical weight: 15.1 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: O60885 (Residues: 44-168; Coverage: 9%)
Gene names: BRD4, HUNK1
Sequence domains: Bromodomain
Structure domains: Bromodomain-like

Ligands and Environments

2 bound ligands:
Ligand L5S 1 x L5S
Ligand EDO 2 x EDO
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ESRF BEAMLINE ID29
Spacegroup: P212121
Unit cell:
a: 37.121Å b: 44.248Å c: 78.47Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.165 0.163 0.186
Expression system: Escherichia coli

Quick links

Citations

49 review citations

Targeting bromodomains: epigenetic readers of lysine acetylation.
Filippakopoulos et al. (2014)
48 more

4 mentions without citation

Discovery and optimization of small-molecule ligands for the CBP/p300 bromodomains.
Hay et al. (2014)
3 more