Medical Molecular Biology Commons^™

Substrate-Specific Effect On Sirtuin Conformation And Oligomerization, Jie Yang, Shannon L. Dwyer, Nathan I. Nicely, Brian P. Weiser

Rowan-Virtua Research Day

Human sirtuins are a family of nicotinamide adenine dinucleotide (NAD +)-dependent enzymes that are responsible for removing acyl modifications from lysine residues. Sirtuins are involved in the formation and proliferation of cancers and are thought to regulate the progression of neurodegenerative diseases. Although sirtuins can be pharmacologically targeted by small molecules, it is not easy to modulate the substrate selectivity of sirtuins despite the chemical diversity of their substrates. Here, we report substrate-specific effects on sirtuin conformation and oligomerization that regulate enzyme deacylase activity. We used fluorescent acyl peptide probes to study substrate interactions with two sirtuin isoforms: SIRT2 and …