Discovery and mechanism study of SIRT1 activators that promote the deacetylation of fluorophore-labeled substrate

…, D Zhang, L Chen, J Li, J Wang, C Ning…

Index: Wu, Jiahui; Zhang, Dengyou; Chen, Lei; Li, Jianneng; Wang, Jianling; Ning, Chengqing; Yu, Niefang; Zhao, Fei; Chen, Dongying; Chen, Xiaoyan; Chen, Kaixian; Jiang, Hualiang; Liu, Hong; Liu, Dongxiang Journal of Medicinal Chemistry, 2013 , vol. 56, # 3 p. 761 - 780

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Citation Number: 17

Abstract

SIRT1 is an NAD+-dependent deacetylase, whose activators have potential therapeutic applications in age-related diseases. Here we report a new class of SIRT1 activators. The activation is dependent on the fluorophore labeled to the substrate. To elucidate the activation mechanism, we solved the crystal structure of SIRT3/ac-RHKKac-AMC complex. The structure revealed that the fluorophore blocked the H-bond formation and created a ...