› 5i8g

X-ray diffraction
1.41Å resolution

CBP in complex with Cpd637 ((R)-4-methyl-6-(1-methyl-3-(1-methyl-1H-pyrazol-4-yl)-1H-indazol-5-yl)-1,3,4,5-tetrahydro-2H-benzo[b][1,4]diazepin-2-one)

Released:
DOI: 10.2210/pdb5i8g/pdb
PDB entry 5i8g coloured by chain, front view.
PDB entry 5i8g coloured by chain, side view.
PDB entry 5i8g coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Fragment-Based Discovery of a Selective and Cell-Active Benzodiazepinone CBP/EP300 Bromodomain Inhibitor (CPI-637).
Taylor AM, Côté A, Hewitt MC, Pastor R, Leblanc Y, Nasveschuk CG, Romero FA, Crawford TD, Cantone N, Jayaram H, Setser J, Murray J, Beresini MH, de Leon Boenig G, Chen Z, Conery AR, Cummings RT, Dakin LA, Flynn EM, Huang OW, Kaufman S, Keller PJ, Kiefer JR, Lai T, Li Y, Liao J, Liu W, Lu H, Pardo E, Tsui V, Wang J, Wang Y, Xu Z, Yan F, Yu D, Zawadzke L, Zhu X, Zhu X, Sims RJ, Cochran AG, Bellon S, Audia JE, Magnuson S, Albrecht BK
ACS Med Chem Lett 7 531-6 (2016)
PMID: 27190605

Function and Biology Details

Reaction catalysed: 
Acetyl-CoA + [protein]-L-lysine = CoA + [protein]-N(6)-acetyl-L-lysine
Biochemical function:
Biological process:
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
CREB-binding protein Chain: A
Molecule details ›
Chain: A
Length: 264 amino acids
Theoretical weight: 31.22 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: Q92793 (Residues: 1081-1312; Coverage: 10%)
Gene names: CBP, CREBBP
Sequence domains:
Structure domains:

Ligands and Environments

6 bound ligands:
Ligand ZN 3 x ZN
Ligand 69E 1 x 69E
Ligand B3P 1 x B3P
Ligand EDO 5 x EDO
Ligand NA 1 x NA
Ligand PEG 2 x PEG
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SSRF BEAMLINE BL17U
Spacegroup: C2
Unit cell:
a: 92.11Å b: 60.06Å c: 54.12Å
α: 90° β: 102.71° γ: 90°
R-values:
R R work R free
0.19 0.189 0.21
Expression system: Escherichia coli

Quick links

Citations

9 review citations

Bromodomain inhibitors and cancer therapy: From structures to applications.
Pérez-Salvia et al. (2017)
8 more

3 mentions without citation

Targeting bromodomain-containing proteins: research advances of drug discovery.
Pan et al. (2023)
2 more