This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Structure of the human Estrogen Receptor Beta (ERb) ligand-binding domain (LBD) Bound to A Family of Compounds with an Oxabicyclic Phenol Scaffold. In May and August 2005, we collected data at the APS on crystal complexes of ERAlpha -LBD bound to compounds with an oxabicyclic phenol scaffold. These compounds vary in their potency and selectivity for ERa and ERb. From these structural data, we can speculate on a possible mode of binding of these compounds to ERb for which they are more selective in solution. We have now crystallized ERb-LBD with these compounds and information from these structures will allow us to design ER subtype-specific ligands using these novel 3D scaffolds for various applications since their biological effects from being full agonists, partial agonists/antagonists, or complete antagonists, depending on the tissue and target gene promoter context. Our interest in these structures is part of our structure-function characterization of the two known ER subtypes. An improved understanding of how this family of compounds binds to ER will allow us to better use this scaffold for the development of improved subtype selective agonists and/or novel antagonists.
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