Structures of human sirtuin 3 complexes with ADP-ribose and with carba-NAD⁺ and SRT1720: binding details and inhibition mechanism

Crystal structures of human Sirt3 ligand complexes, complemented by biochemical analyses, reveal the binding site and mechanism for the small-molecule inhibitor SRT1720. The compound induces a unique co-factor binding-loop conformation and packs sandwich-like between a hydrophobic active-site patch and the nicotinamide moiety of the NAD⁺ cosubstrate.