Journal:JMedChem:1

Structure of estradiol metal chelate and estrogen receptor complex: The basis for designing a new class of SERMs

Min-Jun Li, Harry M. Greenblatt, Orly Dym, Shira Albeck, Adi Pais, Chidambaram Gunanathan, David Milstein, Hadassa Degani, and Joel L. Sussman

Molecular Tour

Selective modulators, such as estradiol 17-derived 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 (ER-LBD) bound with a novel at 2.6 resolution. The residues with estrogen receptor. of this structure with the structure of native ligand 17β-estradiol (E2) in the complex of E2/ERα-LBD complex (1ere) reveals that the . The made by the 17β hydroxyl of E2 with His524 and additional residues e.g. Glu419 of H7 and Glu339 of H3 (this depends on subunit within asymmetric unit), may work together to tighten the neck of the LBP upon binding of the endogenous ligand E2. of EPTA-Eu/ERα-LBD complex on OHT/ERα-LBD complex (3ert). and residues in H3, H7-H8 and H11 within the OHT/ERα-LBD complex. E2/ERα-LBD (1ere), OHT/ERα-LBD (3ert) and EPTA-Eu/ERα-LBD. The structure of estrogen receptor complexed with EPTA-Eu provides important information pertinent to the design of novel functional ER targeted probes for clinical applications.