Polekhina Galina, Gupta Abhilasha, van Denderen Bryce J W, Feil Susanne C, Kemp Bruce E, Stapleton David, Parker Michael W
St. Vincent's Institute of Medical Research, 41 Victoria Parade, Fitzroy, Victoria 3065, Australia.
Structure. 2005 Oct;13(10):1453-62. doi: 10.1016/j.str.2005.07.008.
AMP-activated protein kinase (AMPK) coordinates cellular metabolism in response to energy demand as well as to a variety of stimuli. The AMPK beta subunit acts as a scaffold for the alpha catalytic and gamma regulatory subunits and targets the AMPK heterotrimer to glycogen. We have determined the structure of the AMPK beta glycogen binding domain in complex with beta-cyclodextrin. The structure reveals a carbohydrate binding pocket that consolidates all known aspects of carbohydrate binding observed in starch binding domains into one site, with extensive contact between several residues and five glucose units. beta-cyclodextrin is held in a pincer-like grasp with two tryptophan residues cradling two beta-cyclodextrin glucose units and a leucine residue piercing the beta-cyclodextrin ring. Mutation of key beta-cyclodextrin binding residues either partially or completely prevents the glycogen binding domain from binding glycogen. Modeling suggests that this binding pocket enables AMPK to interact with glycogen anywhere across the carbohydrate's helical surface.
AMP 激活的蛋白激酶（AMPK）可根据能量需求以及各种刺激来协调细胞代谢。AMPK β亚基作为α催化亚基和γ调节亚基的支架，并将AMPK异源三聚体靶向糖原。我们已经确定了与β-环糊精复合的AMPK β糖原结合结构域的结构。该结构揭示了一个碳水化合物结合口袋，它将淀粉结合结构域中观察到的碳水化合物结合的所有已知方面整合到一个位点，几个残基与五个葡萄糖单元之间存在广泛接触。β-环糊精以钳状方式被握住，两个色氨酸残基环抱两个β-环糊精葡萄糖单元，一个亮氨酸残基穿透β-环糊精环。关键的β-环糊精结合残基的突变会部分或完全阻止糖原结合结构域与糖原结合。模型表明，这个结合口袋使AMPK能够在碳水化合物螺旋表面的任何位置与糖原相互作用。
