Structural basis for allosteric, substrate-dependent stimulation of sirt1 activity by resveratrol
文献类型：期刊论文
| 作者 | Cao, Duanfang1,2; Wang, Mingzhu1; Qiu, Xiayang3; Liu, Dongxiang4; Jiang, Hualiang4; Yang, Na1; Xu, Rui-Ming1,2 |
| 刊名 | Genes & development
 |
| 出版日期 | 2015-06-15 |
| 卷号 | 29期号:12页码:1316-1325 |
| 关键词 | Histone/protein deacetylase Resveratrol Sirtuins Structure |
| ISSN号 | 0890-9369 |
| DOI | 10.1101/gad.265462.115 |
| 通讯作者 | Xu, rui-ming(rmxu@ibp.ac.cn) |
| 英文摘要 | Sirtuins with an extended n-terminal domain (ntd), represented by yeast sir2 and human sirt1, harbor intrinsic mechanisms for regulation of their nad-dependent deacetylase activities. elucidation of the regulatory mechanisms is crucial for understanding the biological functions of sirtuins and development of potential therapeutics. in particular, sirt1 has emerged as an attractive therapeutic target, and the search for sirt1-activating compounds (stacs) has been actively pursued. however, the effectiveness of a class of reported stacs (represented by resveratrol) as direct sirt1 activators is under debate due to the complication involving the use of fluorogenic substrates in in vitro assays. future efforts of sirt1-based therapeutics necessitate the dissection of the molecular mechanism of sirt1 stimulation. we solved the structure of sirt1 in complex with resveratrol and a 7-amino-4-methylcoumarin (amc)-containing peptide. the structure reveals the presence of three resveratrol molecules, two of which mediate the interaction between the amc peptide and the ntd of sirt1. the two ntd-bound resveratrol molecules are principally responsible for promoting tighter binding between sirt1 and the peptide and the stimulation of sirt1 activity. the structural information provides valuable insights into regulation of sirt1 activity and should benefit the development of authentic sirt1 activators. |
| WOS关键词 | SMALL-MOLECULE ACTIVATORS ; SILENCING PROTEIN SIR2 ; DEACETYLASE ACTIVITY ; HISTONE DEACETYLASE ; TRANSCRIPTION FACTORS ; CRYSTAL-STRUCTURES ; MECHANISM ; SIRTUINS ; INHIBITION ; P53 |
| WOS研究方向 | Cell Biology ; Developmental Biology ; Genetics & Heredity |
| WOS类目 | Cell Biology ; Developmental Biology ; Genetics & Heredity |
| 语种 | 英语 |
| WOS记录号 | WOS:000356792400009 |
| 出版者 | COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT |
| URI标识 | http://www.irgrid.ac.cn/handle/1471x/2376429 |
| 专题 | 中国科学院大学 |
| 通讯作者 | Xu, Rui-Ming |
| 作者单位 | 1.Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing 100101, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Pfizer Groton Res Labs, Dept Struct Biol & Biophys, Groton, CT 06340 USA 4.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Cao, Duanfang,Wang, Mingzhu,Qiu, Xiayang,et al. Structural basis for allosteric, substrate-dependent stimulation of sirt1 activity by resveratrol[J]. Genes & development,2015,29(12):1316-1325. |
| APA | Cao, Duanfang.,Wang, Mingzhu.,Qiu, Xiayang.,Liu, Dongxiang.,Jiang, Hualiang.,...&Xu, Rui-Ming.(2015).Structural basis for allosteric, substrate-dependent stimulation of sirt1 activity by resveratrol.Genes & development,29(12),1316-1325. |
| MLA | Cao, Duanfang,et al."Structural basis for allosteric, substrate-dependent stimulation of sirt1 activity by resveratrol".Genes & development 29.12(2015):1316-1325. |
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来源：中国科学院大学
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