Researcher(s)
- Lana Kelly, Biochemistry, University of Delaware
Faculty Mentor(s)
- Jeffrey Mugridge, Chemistry & Biochemistry, University of Delaware
Abstract
Elp3 is a radical SAM enzyme that serves as the catalytic core of the multi-subunit eukaryotic Elongator complex, a conserved assembly involved in transcriptional regulation and tRNA modification structurally Elp3 contains two domains: a radical S-adenosylmethionine (SAM) domain, which catalyzes modification of the wobble uridine (U34) position in tRNAs using radical-mediated chemistry, and a lysine acetyl transferase (KAT) domain, which binds to acetyl-CoA to install the 5-carboxymethyl uridine (cm5U) modification necessary for accurate and efficient decoding during translation. Disruptions in Elp3 function have been associated with cancer and neurodegenerative diseases, specifically amyotrophic lateral sclerosis (ALS), showing the biological significance of understanding Elp3’s mechanism.