Structural Basis of Glycogen Biosynthesis Regulation in Bacteria
Structural Basis of Glycogen Biosynthesis Regulation in Bacteria
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DOI：
10.1016/j.str.2016.06.023
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发表时间：
2016-09-06
期刊：
影响因子：
5.7
通讯作者：
Guerin, Marcelo E.
中科院分区：
文献类型：
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作者：
Cifuente, Javier O.;Comino, Natalia;Guerin, Marcelo E.
ADP-葡萄糖焦磷酸化酶(AGPase)催化细菌糖原和植物淀粉生物合成的限速步骤，这是自然界中最常见的碳贮备多糖。一个主要的挑战是了解AGPase活性是如何由细胞内能量流中的代谢物调节的。本文报道了大肠杆菌同源四聚体AGPase与其生理正负变构调节剂、1，6-二磷酸果糖(FBP)和AMP以及活性部位的蔗糖形成的复合体的晶体结构。FBP和AMP结合在邻近原核糖基转移酶A类糖基转移酶和左旋β螺旋区之间的深裂缝中的部分重叠部位，这是因为AMP对抑制的敏感性是由激活剂FBP的浓度调节的。我们提出了一个模型，能量报告者通过原体内相互作用和原体间串扰来调节EcAGPase的催化活性，其中一个感觉基序和两个调控环起着突出的作用。
ADP-glucose pyrophosphorylase (AGPase) catalyzes the rate-limiting step of bacterial glycogen and plant starch biosynthesis, the most common carbon storage polysaccharides in nature. A major challenge is to understand how AGPase activity is regulated by metabolites in the energetic flux within the cell. Here we report crystal structures of the homotetrameric AGPase from Escherichia coli in complex with its physiological positive and negative allosteric regulators, fructose-1,6-bisphosphate (FBP) and AMP, and sucrose in the active site. FBP and AMP bind to partially overlapping sites located in a deep cleft between glycosyltransferase A-like and left-handed beta helix domains of neighboring protomers, accounting for the fact that sensitivity to inhibition by AMP is modulated by the concentration of the activator FBP. We propose a model in which the energy reporters regulate EcAGPase catalytic activity by intra-protomer interactions and inter-protomer crosstalk, with a sensory motif and two regulatory loops playing a prominent role.