Crystal structure of rabbit phosphoglucose isomerase, a glycolytic enzyme that moonlights as neuroleukin, autocrine motility factor, and differentiation mediator
Crystal structure of rabbit phosphoglucose isomerase, a glycolytic enzyme that moonlights as neuroleukin, autocrine motility factor, and differentiation mediator
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DOI：
10.1021/bi991604m
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发表时间：
2000-02-08
期刊：
影响因子：
2.9
通讯作者：
Petsko, A
中科院分区：
文献类型：
--
作者：
Jeffery, CJ;Bahnson, BJ;Petsko, A
多功能蛋白磷酸葡萄糖异构酶，也称为神经白细胞介素、自分泌运动因子和分化成熟介质，在细胞内外具有不同的作用。在细胞质中，它催化糖酵解的第二步。在细胞外，它作为神经生长因子和细胞因子。我们用X射线晶体学方法在2.5埃分辨率下测定了兔肌磷酸葡萄糖异构酶与竞争性抑制剂D-葡萄糖酸6-磷酸复合物的三维结构。结构表明，该酶是一个二聚体，每个亚基中有两个α/β夹心结构域。结合的D-葡萄糖酸6-磷酸抑制剂的位置导致鉴定参与底物特异性的残基（Ser 209、Ser 159、Thr 214、Thr 217和Thr 211）。以前发表的动力学研究的结果表明，赖氨酸和组氨酸参与的催化机制。晶体结构表明活性位点残基Lys 518和His 388可能是这些残基。此外，在遗传性疾病非球形细胞溶血性贫血中被取代的氨基酸残基的位置表明这些取代如何导致催化或蛋白质稳定性的改变。
The multifunctional protein phosphoglucose isomerase, also known as neuroleukin, autocrine motility factor, and differentiation and maturation mediator, has different roles inside and outside the cell. In the cytoplasm, it catalyzes the second step in glycolysis. Outside the cell, it serves as a nerve growth factor and cytokine. We have determined the three-dimensional structure of rabbit muscle phosphoglucose isomerase complexed with the competitive inhibitor D-gluconate 6-phosphate by X-ray crystallography at 2.5 Angstrom resolution. The structure shows that the enzyme is a dimer with two alpha/beta-sandwich domains in each subunit. The location of the bound D-gluconate 6-phosphate inhibitor leads to the identification of residues involved in substrate specificity (Ser209, Ser159, Thr214, Thr217, and Thr211). The results of previously published kinetic studies suggest that a lysine and a histidine are involved in the catalytic mechanism. The crystal structure suggests active site residues Lys518 and His388 might be these residues. In addition, the positions of amino acid residues that are substituted in the genetic disease nonspherocytic hemolytic anemia suggest how these substitutions can result in altered catalysis or protein stability.