Conformational changes in phosphoglucose isomerase induced by ligand binding
Conformational changes in phosphoglucose isomerase induced by ligand binding
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DOI：
10.1016/s0022-2836(02)00892-6
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发表时间：
2002-10-11
影响因子：
5.6
通讯作者：
Jeffery, CJ
中科院分区：
文献类型：
--
作者：
Arsenieva, D;Jeffery, CJ
磷酸葡萄糖异构酶（PGI; EC 5.3.1.9）是糖酵解中的第二种酶，其中它催化D-葡萄糖-6-磷酸异构化为D-果糖-6-磷酸。它与自分泌运动因子、分化和成熟介质以及神经白细胞素是相同的蛋白质。在这里，我们报告了一个新的X-射线晶体结构的兔PGI（rPGI）没有配体结合在其活性位点。该结构通过同晶定相以1.8埃分辨率解析，该同晶定相与先前解析的在其活性位点含有6-磷酸葡萄糖酸盐的rPGI二聚体的X射线晶体结构相同。新结构的比较，以前报道的结构，使识别底物或抑制剂分子结合过程中发生的构象变化。配体结合引起含有氨基酸残基209-215、245-259和385-389的区域的诱导拟合。这种构象变化不同于先前报道的开环和异构化步骤之间发生的变化，其中含有残基513-521的螺旋向结合底物移动。配体和非配体结构之间的差异仅限于活性位点口袋内和附近的区域。(C)2002爱思唯尔科技有限公司。保留所有权利。
Phosphoglucose isomerase (PGI; EC 5.3.1.9) is the second enzyme in glycolysis, where it catalyzes the isomerization of D-glucose-6-phosphate to D-fructose-6-phosphate. It is the same protein as autocrine motility factor, differentiation and maturation mediator, and neuroleukin. Here, we report a new X-ray crystal structure of rabbit PGI (rPGI) without ligands bound in its active site. The structure was solved at 1.8 Angstrom resolution by isomorphous phasing with a previously solved X-ray crystal structure of the rPGI dimer containing 6-phosphogluconate in its active site. Comparison of the new structure to previously reported structures enables identification of conformational changes that occur during binding of substrate or inhibitor molecules. Ligand binding causes an induced fit of regions containing amino acid residues 209-215, 245-259 and 385-389. This conformational change differs from the change previously reported to occur between the ring-opening and isomerization steps, in which the helix containing residues 513-521 moves toward the bound substrate. Differences between the liganded and unliganded structures are limited to the region within and close to the active-site pocket. (C) 2002 Elsevier Science Ltd. All rights reserved.