中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
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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