SIRT7 Is a Lysine Deacylase with a Preference for Depropionylation and Demyristoylation
- Int J Mol Sci. 2025 Mar 28;26(7):3153. doi: 10.3390/ijms26073153.
- 1. Department of Medical Biochemistry, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
- 2. Cell Biology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 606-0823, Japan.
- 3. Center for Integrated Control, Epidemiology and Molecular Pathophysiology of Infectious Diseases, Akita University, Akita 010-8543, Japan.
- 4. Department of Microbiology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
- 5. Center for Metabolic Regulation of Healthy Aging (CMHA), Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
Sirtuins are nicotinamide adenine dinucleotide (NAD+)-dependent deacylases that remove acyl groups from lysine residues on target proteins, releasing nicotinamide. SIRT7 is associated with aging and a number of age-related diseases, but the enzymatic properties of SIRT7 are largely unknown. In the present study, we investigated the biochemical activity of SIRT7 by performing a series of in vitro kinetic studies in the presence of different acyl substrates. The binding affinity of SIRT7 for NAD+ was dependent on the acyl substrate, and SIRT7 showed a preference for depropionylation and demyristoylation. Nicotinamide, the end-product of the Sirtuin reaction, inhibits the activity of SIRT1-6. We also found that the sensitivity of SIRT7 to nicotinamide inhibition also depended on the chain length of the acylated peptides and that nicotinamide was a poor inhibitor of SIRT7 with non-acetylated substrates. These findings may provide insights into the development of novel SIRT7 modulators for the treatment of age-related diseases.