tailieunhanh - Báo cáo khoa học: Small molecule regulation of Sir2 protein deacetylases

The Sir2 family of histone⁄protein deacetylases (sirtuins) is comprised of homologues found across all kingdoms of life. These enzymes catalyse a unique reaction in which NAD + and acetylated substrate are converted into deacetylated product, nicotinamide, and a novel metabolite O-acetyl ADP-ribose. Although the catalytic mechanism is well conserved across Sir2 family members, sirtuins display differential specificity toward acetyl-ated substrates, which translates into an expanding range of physiological functions. . | ềFEBS Journal MINIREVIEW Small molecule regulation of Sir2 protein deacetylases Olivera Grubisha1 Brian C. Smith2 and John M. Denu1 1 Department of Biomolecular Chemistry University of Wisconsin Madison WI USA 2 Department of Chemistry University of Wisconsin Madison WI USA Keywords Sir2 deacetylation sirtuin NAD sirtinol splitomicin resveratrol Correspondence J. M. Denu University of Wisconsin Department of Biomolecular Chemistry 1300 University Ave. Madison WI 53706-1532 USA Fax 1 608 262 5253 Tel 1 608 265 1859 E-mail jmdenu@ Received 17 March 2005 revised 6 June 2005 accepted 8 June 2005 doi The Sir2 family of histone protein deacetylases sirtuins is comprised of homologues found across all kingdoms of life. These enzymes catalyse a unique reaction in which NAD and acetylated substrate are converted into deacetylated product nicotinamide and a novel metabolite O-acetyl ADP-ribose. Although the catalytic mechanism is well conserved across Sir2 family members sirtuins display differential specificity toward acetylated substrates which translates into an expanding range of physiological functions. These roles include control of gene expression cell cycle regulation apoptosis metabolism and ageing. The dependence of sirtuin activity on NAD has spearheaded investigations into how these enzymes respond to metabolic signals such as caloric restriction. In addition NAD metabolites and NAD salvage pathway enzymes regulate sirtuin activity supporting a link between deacetylation of target proteins and metabolic pathways. Apart from physiological regulators forward chemical genetics and high-throughput activity screening has been used to identify sirtuin inhibitors and activators. This review focuses on small molecule regulators that control the activity and functions of this unusual family of protein deacetylases. Introduction The silent information regulator 2 Sir2 family of proteins sirtuins are class III histone protein .

• Báo cáo khoa học
• scientific reports
• Report medicine
• traditional medicine
• oxidation
• chemical reaction
• tumor cells