Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland.
J Mol Biol. 2011 Mar 25;407(2):284-97. doi: 10.1016/j.jmb.2011.01.019. Epub 2011 Jan 15.
Phosphofructokinase 1 (PFK) is a multisubunit allosteric enzyme that catalyzes the principal regulatory step in glycolysis-the phosphorylation of fructose 6-phosphate to fructose 1,6-bisphosphate by ATP. The activity of eukaryotic PFK is modulated by a number of effectors in response to the cell's needs for energy and building blocks for biosynthesis. The crystal structures of eukaryotic PFKs-from Saccharomyces cerevisiae and rabbit skeletal muscle-demonstrate how successive gene duplications and fusion are reflected in the protein structure and how they allowed the evolution of new functionalities. The basic framework inherited from prokaryotes is conserved, and additional levels of structural and functional complexity have evolved around it. Analysis of protein-ligand complexes has shown how PFK is activated by fructose 2,6-bisphosphate (a powerful PFK effector found only in eukaryotes) and reveals a novel nucleotide binding site. Crystallographic results have been used as the basis for structure-based effector design.
磷酸果糖激酶 1（PFK）是一种多亚基变构酶，催化糖酵解的主要调节步骤——由 ATP 将果糖 6-磷酸磷酸化为果糖 1,6-二磷酸。真核生物 PFK 的活性受许多效应物调节，以响应细胞对能量和生物合成构建块的需求。来自酿酒酵母和兔骨骼肌的真核 PFK 的晶体结构展示了连续的基因复制和融合如何反映在蛋白质结构中，以及它们如何允许新功能的进化。从原核生物继承的基本框架得到了保留，并且在其周围进化出了更多层次的结构和功能复杂性。对蛋白-配体复合物的分析表明，PFK 如何被果糖 2,6-二磷酸（一种仅在真核生物中发现的强大 PFK 效应物）激活，并揭示了一个新的核苷酸结合位点。晶体学结果已被用作基于结构的效应物设计的基础。
