Research Assistant University of Detroit Mercy Dearborn, Michigan, United States
Ahed Anbari (University of Detroit Mercy)| Monica Bean (University of Detroit Mercy)| Mara Livezey (University of Detroit Mercy)
BHPI (1,3-Dihydro-3,3-bis(4-hydroxyphenyl)-7-methyl-2H-indol-2-one) is a noncompetitive bio-modulator of estrogen receptor alpha (ERα) that induces necrotic cell death through ATP depletion and has shown promise as a preclinical anticancer drug. BHPI kills cancer cells through activating the anticipatory Unfolded Protein Response (aUPR). The UPR is a stress sensor within the endoplasmic reticulum that is normally a cytoprotective mechanism, but once hyperactivated by BHPI, leads to necrosis. Three ERα PDB structures 1a52, 3ert, and 5u2b were computationally analyzed with a Proline 324 to Alanine (P324A) point mutation to determine where and how BHPI binds to ERα. These studies are important for understanding the effects of amino acid mutations on protein-ligand interaction, as well as the binding affinity of ERα for BHPI.