Mechanism and design of allosteric activators of SIRT1  

作　　者：Fei Liu Ningning Pang Rui-Ming Xu Na Yang 

机构地区：[1]State Key Laboratory of Medicinal Chemical Biology,College of Pharmacy and Key Laboratory of Medical Data Analysis and Statistical Research of Tianjin,Nankai University,Tianjin 300353,China [2]National Laboratory of Biomacromolecules,CAS Center for Excellence in Biomacromolecules,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China

出　　处：《Protein & Cell》2023年第5期387-392,共6页蛋白质与细胞（英文版）

基　　金：the Chinese Ministry of Science and Technology,Natural Science Foundation of China(Grant Nos.2018YFA0107004,2019YFA0508900,91853204,31870737,32170549 and 22103040);the National Postdoctoral Program for Innovative Talents(BX20180149);Haihe Laboratory of Cell Ecosystem Innovation Fund(HH22KYZX0021)and the State Key Laboratory of Medicinal Chemical Biology.

摘　　要：Dear Editor,The sirtuin family Nicotinamide adenine dinucleotide-dependent deacetylases have important roles in many biological processes(Milne and Denu,2008).SIRT1 is a mammalian homolog of yeast Sir2,which is the founding member of the sirtuin family.Many SIRT1 substrates have been reported,including histones,p53,FOXOs,and PGC1α(Hsu et al.,2013).Stimulating the activity of SIRT1 has been shown to be an attractive therapeutic strategy for various physiological and pathological conditions such as aging,metabolic disorders,inflammation,and neurodegeneration(Guarente,2011).Several small molecules have been identified or developed as potential sirtuinactivating compounds(STACs).Most notably,resveratrol,a natural STAC,was shown to activate the SIRT1-catalyzed deacetylation of the Fluor de Lys(FDL)peptide,which is a p53 peptide fused to a 7-amino-4-methylcoumarin(AMC)fluorophore at the C-terminus(Table S1;Howitz et al.,2003).However,the activation of deacetylation of the p53 peptide is dependent on the presence of the AMC fluorophore(Borra et al.,2005;Wu et al.,2013).

关 键 词：SIRT1 PGC1α 

分 类 号：Q5[生物学—生物化学]