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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Near attack conformers dominate p-phosphoglucomutase complexes where geometry and charge distribution reflect those of substrate
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Near attack conformers dominate p-phosphoglucomutase complexes where geometry and charge distribution reflect those of substrate

机译：在构象和电荷分布反映底物的构型和电荷分布的情况下，近攻构象构型占据了p-磷酸葡萄糖变位酶复合物的主导地位。

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摘要

Experimental observations of fluoromagnesate and fluoroalumi-nate complexes of β-phosphoglucomutase (β-PGM) have demonstrated the importance of charge balance in transition-state stabilization for phosphoryl transfer enzymes. Here, direct observations of ground-state analog complexes of p-PGM involving tri-fluoroberyllate establish that when the geometry and charge distribution closely match those of the substrate, the distribution of conformers in solution and in the crystal predominantly places the reacting centers in van der Waals proximity. Importantly, two variants are found, both of which satisfy the criteria for near attack conformers. In one variant, the aspartate general base for the reaction is remote from the nucleophile. The nucleophile remains protonated and forms a nonproductive hydrogen bond to the phosphate surrogate. In the other variant, the general base forms a hydrogen bond to the nucleophile that is now correctly orientated for the chemical transfer step. By contrast, in the absence of substrate, the solvent surrounding the phosphate surrogate is arranged to disfavor nucleophilic attack by water. Taken together, the trif luoroberyllate complexes of (J-PGM provide a picture of how the enzyme is able to organize itself for the chemical step in catalysis through the population of intermediates that respond to increasing proximity of the nucleophile. These experimental observations show how the enzyme is capable of stabilizing the reaction pathway toward the transition state and also of minimizing unproductive catalysis of aspartyl phosphate hydrolysis.
机译：β-磷酸葡糖突变酶（β-PGM）的氟镁酸盐和氟铝酸盐复合物的实验观察表明，电荷平衡对于磷酸转移酶在过渡态稳定中的重要性。在此，对涉及三氟铍酸酯的p-PGM的基态类似物复合物的直接观察发现，当几何结构和电荷分布与底物的几何结构和电荷分布紧密匹配时，构象异构体在溶液中和晶体中的分布主要将反应中心置于van der Waals接近。重要的是，找到了两个变体，它们都满足近距攻击构想者的标准。在一个变体中，该反应的天冬氨酸通用碱基远离亲核试剂。亲核试剂保持质子化并与磷酸盐替代物形成非生产性氢键。在另一个变体中，通用碱基与亲核体形成氢键，该亲核体现在已正确定向用于化学转移步骤。相反，在没有底物的情况下，磷酸盐替代物周围的溶剂被布置为不利于水的亲核攻击。总的来说，（J-PGM）的三氟甲酸酯基复合物提供了一张图片，该酶如何通过对亲核试剂的亲和性不断增加作出响应的中间体群体，能够在催化的化学步骤中组织自身。这些实验观察结果表明，该酶能够稳定反应路径向过渡态的转化，还能够最大程度地减少天冬氨酰磷酸水解的非生产性催化作用。

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    Joanna L Griffin; Matthew W. Bowler; Nicola J. Baxter; Katherine N. Leigh; Hugh R. W. Dannatt; Andrea M. Hounslow; G. Michael Blackburn; Charles Edwin Webster; Matthew J. Cliff; Jonathan P. Waltho;

  • 作者单位

    Department of Molecular Biology and Biotechnology, Krebs Institute, University of Sheffield, Sheffield S10 2TN, United Kingdom;

    Structural Biology Group,European Synchrotron Radiation Facility, F-38043 Grenoble Cedex, France;

    Manchester Interdisciplinary Biocentre, University of Manchester, Manchester M1 7DN, United Kingdom;

    Department of Chemistry, University of Memphis, Memphis, TN 38152-3550;

    Department of Molecular Biology and Biotechnology, Krebs Institute, University of Sheffield, Sheffield S10 2TN, United Kingdom;

    Department of Molecular Biology and Biotechnology, Krebs Institute, University of Sheffield, Sheffield S10 2TN, United Kingdom;

    Department of Molecular Biology and Biotechnology, Krebs Institute, University of Sheffield, Sheffield S10 2TN, United Kingdom;

    Department of Chemistry, University of Memphis, Memphis, TN 38152-3550;

    Department of Molecular Biology and Biotechnology, Krebs Institute, University of Sheffield, Sheffield S10 2TN, United Kingdom;

    Department of Molecular Biology and Biotechnology, Krebs Institute, University of Sheffield, Sheffield S10 2TN, United Kingdom,Manchester Interdisciplinary Biocentre, University of Manchester, Manchester M1 7DN, United Kingdom;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    ground-state analogues; enzyme mechanism;

    机译：基态类似物;酶机制;

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