Abstract
Human histone lysine-specific demethylase 1 (LSD1) is an epigenetics-associated flavin-dependent amine oxidase that catalyzes the removal of methyl groups from lysine 4 of histone 3. Catalytic activity by LSD1 can lead to gene silencing and ultimately result in severe consequences such as cancer progression. This talk will focus on the discovery and chemical mechanism of LSD1, the interaction of LSD1 with the corepressor protein CoREST, the enzymatic reaction mechanism of LSD1-catalyzed oxidative demethylation, the chemical synthesis of small molecule mechanism-based inactivators of LSD1 and the analysis of their inhibitory activity toward the enzyme in vitro and in cellulo.
