Forskning ved Københavns Universitet - Københavns Universitet


Targeting Sirtuins: Substrate Specificity and Inhibitor Design

Publikation: Bidrag til bog/antologi/rapportBidrag til bog/antologiForskning

Lysine residues across the proteome are modified by posttranslational modifications (PTMs) that significantly enhance the structural and functional diversity of proteins. For lysine, the most abundant PTM is ɛ-N-acetyllysine (Kac), which plays numerous roles in regulation of important cellular functions, such as gene expression (epigenetic effects) and metabolism. A family of enzymes, namely histone deacetylases (HDACs), removes these PTMs. A subset of these enzymes, the sirtuins (SIRTs), represent class III HDAC and, unlike the rest of the family, these hydrolases are NAD+-dependent. Although initially described as deacetylases, alternative deacylase functions for sirtuins have been reported, which expands the potential cellular roles of this class of enzymes. Currently, sirtuins are investigated as therapeutic targets for the treatment of diseases that span from cancers to neurodegenerative disorders. In the present book chapter, we review and discuss the current literature on novel ɛ-N-acyllysine PTMs, targeted by sirtuins, as well as mechanism-based sirtuin inhibitors inspired by their substrates.
TitelProgress in Molecular Biology and Translational Science : Sirtuins in Health and Disease
Publikationsdato3 feb. 2018
StatusUdgivet - 3 feb. 2018
NavnProgress in Molecular Biology and Translational Science

ID: 199215102