› 5t92

X-ray diffraction
2.22Å resolution

ESTROGEN RECEPTOR ALPHA LIGAND BINDING DOMAIN IN COMPLEX WITH (2E)-3-{4-[(1R)-2-(4-fluorophenyl)-6-hydroxy-1-methy l-1,2,3,4- tetrahydroisoquinolin-1-yl]phenyl}prop-2-enoic acid

Released:
DOI: 10.2210/pdb5t92/pdb
PDB entry 5t92 coloured by chain, front view.
PDB entry 5t92 coloured by chain, side view.
PDB entry 5t92 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of an Acrylic Acid Based Tetrahydroisoquinoline as an Orally Bioavailable Selective Estrogen Receptor Degrader for ERα+ Breast Cancer.
Burks HE, Abrams T, Kirby CA, Baird J, Fekete A, Hamann LG, Kim S, Lombardo F, Loo A, Lubicka D, Macchi K, McDonnell DP, Mishina Y, Norris JD, Nunez J, Saran C, Sun Y, Thomsen NM, Wang C, Wang J, Peukert S
J Med Chem 60 2790-2818 (2017)
PMID: 28296398

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)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Estrogen receptor Chains: A, B
Molecule details ›
Chains: A, B
Length: 254 amino acids
Theoretical weight: 28.9 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P03372 (Residues: 301-553; Coverage: 43%)
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 77W 2 x 77W
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 17-ID
Spacegroup: C2
Unit cell:
a: 105.22Å b: 53.89Å c: 97.11Å
α: 90° β: 114.11° γ: 90°
R-values:
R R work R free
0.242 0.24 0.282
Expression system: Escherichia coli

Quick links

Citations

2 review citations

Recent progress in selective estrogen receptor downregulators (SERDs) for the treatment of breast cancer.
Shagufta et al. (2020)
1 more

1 mention without citation

Stereospecific lasofoxifene derivatives reveal the interplay between estrogen receptor alpha stability and antagonistic activity in ESR1 mutant breast cancer cells.
Hosfield et al. (2022)