Interactions of SIRT1 with Acetyl Substrate, NAD~+ or Nicotinamide
文献类型：期刊论文
| 作者 | Qin Yutao1; Xiao Wen1; Feng Yu2; Liu Dongxiang1 ; Tang Yun1
|
| 刊名 | Journal of East China University of Science and Technoloy. Natural Sciences Edition
 |
| 出版日期 | 2013 |
| 卷号 | 39期号:4页码:405-414 |
| 关键词 | SIRT1 NAD~+ SIRT1 protein deacetylation NAD~+ inhibitor nicotinamide |
| ISSN号 | 1006-3080 |
| 其他题名 | SIRT1与乙酰化底物、NAD~+或烟酰胺的相互作用 |
| 文献子类 | Article |
| 英文摘要 | SIRT1 is a NAD~+ dependent protein deacetylase. Nicotinamide is a reaction product of the SIRT1 catalyzed deacetylation and also a noncompetitive inhibitor of SIRT1. Here we built the complex structures of SIRT1/NAD~+/p53 acetyl peptide and SIRT1/ADPR/nicotinamide by protein homology modeling and molecular docking. According to the docking results, S265 and N346 of SIRT1 are involved in the interactions with NAD~+, while S275 is at the entrance of the NAD~+ binding pocket. Consistently, our enzyme kinetics studies proved that mutations of S265, S275 or N346 either reduced or destroyed the interaction of NAD+ with SIRT1. In addition, the carboxamide group of nicotinamide forms hydrogen bonds with I347 and D348, while the pyridine ring is buried in a hydrophobic environment surrounded by A262, I270, F273, I316 and I347. Interestingly, mutation of I316 to alanine increased the affinity of nicotinamide and dramatically improved its inhibitory activity, indicating that nicotinamide binds in the C pocket of SIRT1. |
| WOS研究方向 | Biochemistry & Molecular Biology (provided by Clarivate Analytics) |
| 语种 | 中文 |
| CSCD记录号 | CSCD:4921132 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/267761]  |
| 专题 | 药理学第三研究室 药物发现与设计中心 |
| 通讯作者 | Liu Dongxiang |
| 作者单位 | 1.School of Pharmacy,East China University of Science and Technology, Shanghai 200237, China.; 2.Shanghai Institute of Materia Medica,Chinese Academy of Sciences, Shanghai 201203, China. |
| 推荐引用方式 GB/T 7714 | Qin Yutao,Xiao Wen,Feng Yu,et al. Interactions of SIRT1 with Acetyl Substrate, NAD~+ or Nicotinamide[J]. Journal of East China University of Science and Technoloy. Natural Sciences Edition,2013,39(4):405-414. |
| APA | Qin Yutao,Xiao Wen,Feng Yu,Liu Dongxiang,&Tang Yun.(2013).Interactions of SIRT1 with Acetyl Substrate, NAD~+ or Nicotinamide.Journal of East China University of Science and Technoloy. Natural Sciences Edition,39(4),405-414. |
| MLA | Qin Yutao,et al."Interactions of SIRT1 with Acetyl Substrate, NAD~+ or Nicotinamide".Journal of East China University of Science and Technoloy. Natural Sciences Edition 39.4(2013):405-414. |
入库方式： OAI收割
来源：上海药物研究所
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