Structural basis of AMPK regulation by adenine nucleotides and glycogen

查看全文 作　　者：Xiaodan [1,2,3]Li;Lili [1,2,3]Wang;X Edward [3]Zhou;Jiyuan [3]Ke;Parker W de [3]Waal;Xin [3]Gu;M H Eileen [3,4]Tan;Dongye [1]Wang;Donghai [1]Wu;H Eric [3,5]Xu;Karsten [3]Melcher

机构地区：[1]Key Laboratory of Regenerative Biology, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guang- zhou, Guangdong 510530, China;[2]School of Life Science, University of Science and Technology of China, Hefei, Anhui 230027, China;[3]Laboratory of Structural Sciences, Van Andel Research Institute, 333 Bostwick Ave, NE, Grand Rapids, MI 49503, USA;[4]Department of Obstetrics & Gynecology, National University Hospital, Yong Loo Lin School of Medicine, National University of Singapore, 119074, Singapore;[5]VARI/SIMM Center, CAS-Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China

出　　处：《Cell Research》索引2015年第25卷第1期,共17页

基　　金：This work was supported by Van Andel Research Institute (HEX and KM), by the National Institute of Health (grant R01 GM104212 to KM), by the National Basic Research Program of China (973 Program; 2011CB504004 and 2010CB945500 to D Wu), by the National Natural Science Foundation of China (to D Wang) and by an overseas PhD scholarship from the National University of Singapore to MHET. We thank Stephanie Grant for administrative support and staff members of the Life Science Collaborative Access Team of the Advanced Photon Source (APS) for assistance in data collection at the beam lines of sector 21, which is in part funded by the Michigan Economic Development Corporation and the Michigan Technology Tri-Corridor (Grant 085P1000817). Use of APS was supported by the Office of Science of the US Department of Energy, under contract no. DEAC02-06CH11357. 摘　　要：激活安培的蛋白质 kinase (AMPK ) 为糖尿病,肥胖,和癌症的治疗是一个中央细胞的精力传感器和精力动态平衡,和一个有希望的药目标的管理者。这里我们人的 α 的现在的低分辨率的水晶结构; 1 β 2 γ 1 holo-AMPK 建筑群跳了到它的 allosteric 调节的人安培和肝糖模仿 cyclodextrin,两个在 phosphorylated (4.05 Å) 并且 non-phosphorylated (4.60 Å) 状态。另外,我们解决了 2.95 Å人的 kinase 领域(KD ) 的结构跳了到邻近的 autoinhibitory 领域(帮助) 并且表现了广泛生物化学并且 mutational 研究。一起,这些研究由安培和肝糖说明 allosteric AMPK 调整的内在的机制,其绑定改变在交替的帮助(安培) 和糖类绑定模块(肝糖) 之间的 equilibria 相互作用。 关键词：AMPK 结构基础糖原腺苷酸调控蛋白激酶中央细胞药物靶标

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Structural basis of AMPK regulation by adenine nucleotides and glycogen

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