Dual role of Zn2+ in maintaining structural integrity and suppressing deacetylase activity of SIRT1
文献类型：期刊论文
| 作者 | Chen, Lei2; Feng, Yu2; Zhou, Yinqiu3; Zhu, Weiliang1 ; Shen, Xu2; Chen, Kaixian1; Jiang, Hualiang1,3; Liu, Dongxiang2
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| 刊名 | JOURNAL OF INORGANIC BIOCHEMISTRY
 |
| 出版日期 | 2010-02 |
| 卷号 | 104期号:2页码:180-185 |
| 关键词 | Zinc ion SIRT1 Protein deacetylation Zinc-finger motif Noncompetitive inhibitor |
| ISSN号 | 0162-0134 |
| DOI | 10.1016/j.jinorgbio.2009.10.021 |
| 文献子类 | Article |
| 英文摘要 | Zn2+ directly participates in catalysis of histone deacetylase (HDAC) Classes I, II, IV enzymes while its role in HDAC Class III activity is not well established. Herein we investigated the effects of Zn2+ on the deacetylase activity of sirtuin 1 (silent mating type information regulation 2 homolog 1, SIRT1). We found that the inherent Zn2+ at the zinc-finger motif of SIRT1 is essential for the structural integrity and the deacetylase activity of SIRT1, whereas the exogenous Zn2+ strongly inhibits the deacetylase activity with an IC50 of 0.82 mu M for Zn(Gly)(2). SIRT1 activity suppressed by the exogenous Zn2+ can be fully recovered by the metal chelator EDTA but not by the activator resveratrol. We also identified Zn2+ as a noncompetitive inhibitor for the substrates of NAD(+) and the acetyl peptide P53-AMC. The 8-anilino-1-naphthalenesulfonic acid (ANS) fluorescence titration experiments and site-directed mutagenesis study suggested that the exogenous Zn2+ binds to SIRT1 but not at the zinc-finger motif. These results indicate that Zn2+ plays a dual role in SIRT1 activity. Inherent Zn2+ at the zinc-finger motif is structurally related and essential for SIRT1 activity. On the other hand, Zn2+ may also bind to another site different from the zinc-finger motif or the binding sites for the substrates or resveratrol and act as a potent inhibitor of SIRT1. (C) 2009 Elsevier Inc. All rights reserved. |
| WOS关键词 | SMALL-MOLECULE ACTIVATORS ; CELL-SURVIVAL ; TRANSCRIPTION ; MECHANISM ; SIRTUINS ; ZINC ; INHIBITION ; STRESS ; FAMILY ; ENZYME |
| 资助项目 | Shanghai Basic Science Priority Research Program[08JC1422100] ; CAS Introducing Outstanding Oversea Scientists Project[00000000] ; NSFC Innovation Program for Research Group[20721003] ; State Key Laboratory of Drug Research[00000000] ; National Science and Technology Major Project[2009ZX09301-001] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000273448100011 |
| 出版者 | ELSEVIER SCIENCE INC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278983]  |
| 专题 | 药理学第三研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Liu, Dongxiang |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Design & Discovery, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Mol Pharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 3.E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China |
| 推荐引用方式 GB/T 7714 | Chen, Lei,Feng, Yu,Zhou, Yinqiu,et al. Dual role of Zn2+ in maintaining structural integrity and suppressing deacetylase activity of SIRT1[J]. JOURNAL OF INORGANIC BIOCHEMISTRY,2010,104(2):180-185. |
| APA | Chen, Lei.,Feng, Yu.,Zhou, Yinqiu.,Zhu, Weiliang.,Shen, Xu.,...&Liu, Dongxiang.(2010).Dual role of Zn2+ in maintaining structural integrity and suppressing deacetylase activity of SIRT1.JOURNAL OF INORGANIC BIOCHEMISTRY,104(2),180-185. |
| MLA | Chen, Lei,et al."Dual role of Zn2+ in maintaining structural integrity and suppressing deacetylase activity of SIRT1".JOURNAL OF INORGANIC BIOCHEMISTRY 104.2(2010):180-185. |
入库方式： OAI收割
来源：上海药物研究所
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