Elucidation of the inhibitory mechanism of a lysine deacetylase Siruin by endogenous metabolites

2015 Fiscal Year Final Research Report

• Project/Area Number: 26650011
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Molecular biology
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Ito Akihiro 国立研究開発法人理化学研究所, 吉田化学遺伝学研究室, 専任研究員 (40391859)
• Co-Investigator(Renkei-kenkyūsha): Moto Kenichi 国立研究開発法人理化学研究所, 小林脂質生物学研究室, 専任研究員 (90333335) ; Kudo Norio 国立研究開発法人理化学研究所, 環境資源科学研究センター, 研究員 (80632421)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: Sirtuin / 代謝物質 / アセチル化

Outline of Final Research Achievements

Sirtuins possess NAD-dependent deacetylase activity and is involved in diverse biological processes including aging. The enzymatic activity of sirtuins is known to be regulated by cellular NAD/NADH ratio. However, endogenous inhibitors for sirtuins have not been identified yet. Here, we identified N-acyldopamines as endogenous SIRT2 inhibitors. We found that a number of N-acyldopamine species including N-palmitoyldopamine inhibit both in vitro and in vivo SIRT2 activity. In addition, X-ray crystallographic analysis of the SIRT2―N-palmitoyldopamine complex revealed the molecular mechanism by which N-acyldopamines inhibit the SIRT2 activity.

Free Research Field

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