Polekhina Galina, Feil Susanne C, Gupta Abhilasha, O'Donnell Paul, Stapleton David, Parker Michael W
St Vincent's Institute of Medical Research, Fitzroy, Victoria 3065, Australia.
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2005 Jan 1;61(Pt 1):39-42. doi: 10.1107/S1744309104025059. Epub 2004 Oct 9.
AMP-activated protein kinase (AMPK) is an intracellular energy sensor that regulates metabolism in response to energy demand and supply by adjusting the ATP-generating and ATP-consuming pathways. AMPK potentially plays a critical role in diabetes and obesity as it is known to be activated by metforin and rosiglitazone, drugs used for the treatment of type II diabetes. AMPK is a heterotrimer composed of a catalytic alpha subunit and two regulatory subunits, beta and gamma. Mutations in the gamma subunit are known to cause glycogen accumulation, leading to cardiac arrhythmias. Recently, a functional glycogen-binding domain (GBD) has been identified in the beta subunit. Here, the crystallization of GBD in the presence of beta-cyclodextrin is reported together with preliminary X-ray data analysis allowing the determination of the structure by single isomorphous replacement and threefold averaging using in-house X-ray data collected from a selenomethionine-substituted protein.
AMP激活的蛋白激酶（AMPK）是一种细胞内能量传感器，通过调节ATP生成和消耗途径来响应能量需求和供应，从而调节新陈代谢。AMPK可能在糖尿病和肥胖症中起关键作用，因为已知它可被用于治疗II型糖尿病的药物二甲双胍和罗格列酮激活。AMPK是一种异源三聚体，由一个催化性α亚基和两个调节性亚基β和γ组成。已知γ亚基的突变会导致糖原积累，进而引发心律失常。最近，在β亚基中鉴定出了一个功能性糖原结合结构域（GBD）。本文报道了β-环糊精存在下GBD的晶体化情况，并进行了初步的X射线数据分析，通过单同晶置换和三重平均法，利用从硒代蛋氨酸取代的蛋白质收集的内部X射线数据确定其结构。
