The role of structural biology in the design of sirtuin activators.

Francesco Fiorentino, Antonello Mai, Dante Rotili

Current opinion in structural biology 2023 Oct

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Sirtuins are NAD+-dependent protein lysine deacylases and mono-ADP-ribosylases whose activity regulates different pathways, including DNA damage repair, cell survival and metabolism, reactive oxygen species (ROS) detoxification, inflammation, cardiac function, and neuronal signaling. Considering the beneficial effects of specific sirtuin isoforms on health and lifespan, the past two decades have seen a mounting interest in the development of sirtuin activators. The availability of enzyme-activator co-crystal structures has proven significant throughout the years for elucidating the mechanisms of action of activators and designing more potent and selective molecules. In this review, we highlight the most interesting examples of sirtuin activators and provide comprehensive coverage of the role that structural biology played in their discovery and characterization. Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.

Citation

Francesco Fiorentino, Antonello Mai, Dante Rotili. The role of structural biology in the design of sirtuin activators. Current opinion in structural biology. 2023 Oct;82:102666