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

…, D Chen, X Chen, K Chen, H Jiang, H Liu…

Index: He, Lingyan; Zhang, Liang; Liu, Xiaofeng; Li, Xianghua; Zheng, Mingyue; Li, HongLin; Yu, Kunqian; Chen, Kaixian; Shen, Xu; Jiang, Hualiang; Liu, Hong Journal of Medicinal Chemistry, 2009 , vol. 52, # 8 p. 2465 - 2481

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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 ...