3,3-bis(4-hydroxyphenyl)-7-methyl-1,3,dihydro-2H-indol-2-one (BHPI) is a biomodulator of Estrogen Receptor alpha (ERα) that targets ERα positive cancer cells by activating the unfolded protein response (UPR). BHPI induces strong and sustained activation of this pathway, eventually resulting in necrotic cell death. While much is known about how BHPI triggers the UPR leading to necrotic cell death, it is not known how BHPI binds to its putative molecular target, ERα. In an effort to identify the binding site of BHPI on ERα, molecular docking studies in AutoDock Vina were utilized. Unexpectedly, BHPI was found to dock more frequently and with significantly better binding affinity to a newly described surface pocket on the ERα ligand-binding domain, compared to the ligand-binding pocket. This work uncovers a novel binding site for small molecules on ERα that is not targeted by classical ligands, such as estrogen and tamoxifen, and may allow for the design of additional anti-cancer drugs that work in distinct ways.
Estrogen Receptor alpha , Tamoxifen , Binding Sites , Estrogen Receptor alpha/metabolism , Ligands , Molecular Docking Simulation , Protein Binding , Tamoxifen/pharmacology
Mycobacteriophages Darionha, Salz, and ThreeRngTarjay are mycobacteriophages isolated using the host Mycobacterium smegmatis mc2155. Following isolation from soil samples, all three siphoviridae phages were characterized, and their genomes were sequenced and annotated.
