› 5aav

X-ray diffraction
1.95Å 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/pdb5aav/pdb
PDB entry 5aav coloured by chain, front view.
PDB entry 5aav coloured by chain, side view.
PDB entry 5aav 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:
hetero dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-136904 (preferred)
Entry contents:
2 distinct polypeptide molecules
Macromolecules (2 distinct):
Estrogen receptor Chain: A
Molecule details ›
Chain: A
Length: 252 amino acids
Theoretical weight: 28.66 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
Estrogen receptor Chain: B
Molecule details ›
Chain: B
Length: 252 amino acids
Theoretical weight: 28.64 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: P03372 (Residues: 306-554; 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 GW5 2 x GW5
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: DIAMOND BEAMLINE I04
Spacegroup: C2
Unit cell:
a: 105.488Å b: 51.54Å c: 83.705Å
α: 90° β: 90.9° γ: 90°
R-values:
R R work R free
0.198 0.196 0.234
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

19 review citations

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

3 mentions without citation

Exploring the mechanism of hirudin in the treatment of diabetic kidney disease using network pharmacology combined with molecular docking verification.
Xinxin et al. (2022)
2 more