Structural basis of AMPK regulation by adenine nucleotides and glycogen
文献类型：期刊论文
| 作者 | Li, Xiaodan1,2,5; Wang, Lili1,2,5; Zhou, X. Edward2; Ke, Jiyuan2; de Waal, Parker W.2; Gu, Xin2; Tan, M. H. Eileen2,3; Wang, Dongye1; Wu, Donghai1; Xu, H. Eric2,4
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| 刊名 | CELL RESEARCH
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| 出版日期 | 2015-01 |
| 卷号 | 25期号:1页码:50-66 |
| ISSN号 | 1001-0602 |
| 关键词 | AMPK adenine nucleotides glycogen diabetes |
| DOI | 10.1038/cr.2014.150 |
| 文献子类 | Article |
| 英文摘要 | AMP-activated protein kinase (AMPK) is a central cellular energy sensor and regulator of energy homeostasis, and a promising drug target for the treatment of diabetes, obesity, and cancer. Here we present low-resolution crystal structures of the human alpha 1 gamma 2.1 holo-AMPK complex bound to its allosteric modulators AMP and the glycogen-mimic cyclodextrin, both in the phosphorylated (4.05 angstrom) and non-phosphorylated (4.60 angstrom) state. In addition, we have solved a 2.95 angstrom structure of the human kinase domain (KD) bound to the adjacent autoinhibitory domain (AID) and have performed extensive biochemical and mutational studies. Together, these studies illustrate an underlying mechanism of allosteric AMPK modulation by AMP and glycogen, whose binding changes the equilibria between alternate AID (AMP) and carbohydrate-binding module (glycogen) interactions. |
| WOS关键词 | ACTIVATED PROTEIN-KINASE ; ACETYL-COA CARBOXYLASE ; UPSTREAM KINASE ; ESCHERICHIA-COLI ; ENERGY-CHARGE ; RAT-LIVER ; SUBUNIT ; BETA ; PHOSPHORYLATION ; STRESS |
| 资助项目 | Van Andel Research Institute[00000000] ; National Institute of Health[R01 GM104212] ; National Basic Research Program of China (973 Program)[2011CB504004] ; National Basic Research Program of China (973 Program)[2010CB945500] ; National Natural Science Foundation of China[00000000] ; National University of Singapore[00000000] ; Stephanie Grant[00000000] ; Michigan Economic Development Corporation[00000000] ; Michigan Technology Tri-Corridor[085P1000817] ; Office of Science of the US Department of Energy[DE-AC02-06CH11357] |
| WOS研究方向 | Cell Biology |
| 语种 | 英语 |
| 出版者 | INST BIOCHEMISTRY & CELL BIOLOGY |
| WOS记录号 | WOS:000349330800008 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276760]  |
| 专题 | 药物靶标结构与功能中心 |
| 通讯作者 | Melcher, Karsten |
| 作者单位 | 1.Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Key Lab Regenerat Biol, Guangzhou 510530, Guangdong, Peoples R China; 2.Van Andel Res Inst, Lab Struct Sci, Grand Rapids, MI 49503 USA; 3.Natl Univ Singapore, Natl Univ Hosp, Yong Loo Lin Sch Med, Dept Obstet & Gynecol, Singapore 119074, Singapore; 4.Chinese Acad Sci, Shanghai Inst Mat Med, VARI SIMM Ctr, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China 5.Univ Sci & Technol China, Sch Life Sci, Hefei 230027, Anhui, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Li, Xiaodan,Wang, Lili,Zhou, X. Edward,et al. Structural basis of AMPK regulation by adenine nucleotides and glycogen[J]. CELL RESEARCH,2015,25(1):50-66. |
| APA | Li, Xiaodan.,Wang, Lili.,Zhou, X. Edward.,Ke, Jiyuan.,de Waal, Parker W..,...&Melcher, Karsten.(2015).Structural basis of AMPK regulation by adenine nucleotides and glycogen.CELL RESEARCH,25(1),50-66. |
| MLA | Li, Xiaodan,et al."Structural basis of AMPK regulation by adenine nucleotides and glycogen".CELL RESEARCH 25.1(2015):50-66. |
入库方式： OAI收割
来源：上海药物研究所
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