title: Structure of estradiol metal chelate and estrogen receptor complex: the basis for designing a new class of selective estrogen receptor modulators.
abstract: Selective estrogen receptor modulators, such as 17β-estradiol derivatives bound to metal complexes, have been synthesized as targeted probes for the diagnosis and treatment of breast cancer. Here, we report the detailed 3D structure of estrogen receptor α ligand-binding domain (ERα-LBD) bound with a novel estradiol-derived metal complex, estradiol-pyridine tetra acetate europium(III), at 2.6 Å resolution. This structure provides important information pertinent to the design of novel functional ERα targeted probes for clinical applications.
authors.affiliation: Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Min-Jun
authors.initials: MJ
authors.lastname: Li
authors.forename: Harry M
authors.initials: HM
authors.lastname: Greenblatt
authors.forename: Orly
authors.initials: O
authors.lastname: Dym
authors.forename: Shira
authors.initials: S
authors.lastname: Albeck
authors.forename: Adi
authors.initials: A
authors.lastname: Pais
authors.forename: Chidambaram
authors.initials: C
authors.lastname: Gunanathan
authors.forename: David
authors.initials: D
authors.lastname: Milstein
authors.forename: Hadassa
authors.initials: H
authors.lastname: Degani
authors.forename: Joel L
authors.initials: JL
authors.lastname: Sussman
mesh_terms: D002614:Chelating Agents / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D018360:Crystallography, X-Ray / Q000379:methods; D019281:Dimerization; D004958:Estradiol / Q000737:chemistry*; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors*; D005063:Europium / Q000737:chemistry; D006801:Humans; D008024:Ligands; D008670:Metals / Q000737:chemistry*; D008956:Models, Chemical; D008968:Molecular Conformation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D020845:Selective Estrogen Receptor Modulators / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D002614:Chelating Agents; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D008024:Ligands; D008670:Metals; D020845:Selective Estrogen Receptor Modulators; D005063:Europium; D004958:Estradiol