2. Academic Validation
  3. SIRT7 Is a Lysine Deacylase with a Preference for Depropionylation and Demyristoylation

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.
Mohammad Golam Kibria 1,  Tatsuya Yoshizawa 1 2,  Tianli Zhang 3,  Katsuhiko Ono 4,  Tomoya Mizumoto 1,  Yoshifumi Sato 1,  Tomohiro Sawa 4,  Kazuya Yamagata 1 5
Affiliations

Affiliations

  • 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.
PMID: 40243935 DOI: 10.3390/ijms26073153
Abstract

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.

Keywords

NAD+; SIRT7; deacetylation; deacylation; nicotinamide; sirtuin.

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