› 5ku3

X-ray diffraction
1.14Å resolution

BRD4 bromodomain in complex with Cpd59 ((S)-1-(3-((2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)phenyl)amino)-1-(tetrahydrofuran-3-yl)-6,7-dihydro-1H-pyrazolo[4,3-c]pyridin-5(4H)-yl)ethanone)

Released:
DOI: 10.2210/pdb5ku3/pdb
PDB entry 5ku3 coloured by chain, front view.
PDB entry 5ku3 coloured by chain, side view.
PDB entry 5ku3 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of a Potent and Selective in Vivo Probe (GNE-272) for the Bromodomains of CBP/EP300.
Crawford TD, Romero FA, Lai KW, Tsui V, Taylor AM, de Leon Boenig G, Noland CL, Murray J, Ly J, Choo EF, Hunsaker TL, Chan EW, Merchant M, Kharbanda S, Gascoigne KE, Kaufman S, Beresini MH, Liao J, Liu W, Chen KX, Chen Z, Conery AR, Côté A, Jayaram H, Jiang Y, Kiefer JR, Kleinheinz T, Li Y, Maher J, Pardo E, Poy F, Spillane KL, Wang F, Wang J, Wei X, Xu Z, Xu Z, Yen I, Zawadzke L, Zhu X, Bellon S, Cummings R, Cochran AG, Albrecht BK, Magnuson S
J Med Chem 59 10549-10563 (2016)
PMID: 27682507

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: 126 amino acids
Theoretical weight: 14.94 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: O60885 (Residues: 42-167; Coverage: 9%)
Gene names: BRD4, HUNK1
Sequence domains: Bromodomain
Structure domains: Bromodomain-like

Ligands and Environments

5 bound ligands:
Ligand EDO 6 x EDO
Ligand DMS 2 x DMS
Ligand GOL 1 x GOL
Ligand PEG 1 x PEG
Ligand 6XH 1 x 6XH
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SSRF BEAMLINE BL19U1
Spacegroup: C2221
Unit cell:
a: 46.037Å b: 53.115Å c: 106.745Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.164 0.164 0.182
Expression system: Escherichia coli

Quick links

Citations

9 review citations

Lysine Acetylation Goes Global: From Epigenetics to Metabolism and Therapeutics.
Ali et al. (2018)
8 more

3 mentions without citation

Discovery of Orally Bioavailable Chromone Derivatives as Potent and Selective BRD4 Inhibitors: Scaffold Hopping, Optimization, and Pharmacological Evaluation.
Liu et al. (2020)
2 more