› 5aau

X-ray diffraction
1.9Å resolution

Optimization of a novel binding motif to to (E)-3-(3,5-difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H- pyrido(3,4-b)indol-1-yl)phenyl)acrylic acid (AZD9496), a potent and orally bioavailable selective estrogen receptor downregulator and antagonist

Released:
DOI: 10.2210/pdb5aau/pdb
PDB entry 5aau coloured by chain, front view.
PDB entry 5aau coloured by chain, side view.
PDB entry 5aau coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Optimization of a Novel Binding Motif to (E)-3-(3,5-Difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylic Acid (AZD9496), a Potent and Orally Bioavailable Selective Estrogen Receptor Downregulator and Antagonist.
De Savi C, Bradbury RH, Rabow AA, Norman RA, de Almeida C, Andrews DM, Ballard P, Buttar D, Callis RJ, Currie GS, Curwen JO, Davies CD, Donald CS, Feron LJ, Gingell H, Glossop SC, Hayter BR, Hussain S, Karoutchi G, Lamont SG, MacFaul P, Moss TA, Pearson SE, Tonge M, Walker GE, Weir HM, Wilson Z
J Med Chem 58 8128-40 (2015)
PMID: 26407012

Function and Biology Details

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

Structure analysis Details

Assembly composition:
homo dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-136919 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Estrogen receptor Chains: A, B
Molecule details ›
Chains: A, B
Length: 252 amino acids
Theoretical weight: 28.67 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: P03372 (Residues: 307-554; Coverage: 42%)
Gene names: ESR, ESR1, NR3A1
Sequence domains: Ligand-binding domain of nuclear hormone receptor
Structure domains: Retinoid X Receptor

Ligands and Environments

1 bound ligand:
Ligand XBR 2 x XBR
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: DIAMOND BEAMLINE I04
Spacegroup: C2
Unit cell:
a: 106.407Å b: 51.396Å c: 85.181Å
α: 90° β: 93.66° γ: 90°
R-values:
R R work R free
0.176 0.173 0.226
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

19 review citations

Targeted Protein Degradation by Small Molecules.
Bondeson et al. (2017)
18 more

1 mention without citation

Molecular Anatomy of the EML4-ALK Fusion Protein for the Development of Novel Anticancer Drugs.
Cheon et al. (2023)