...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biochemistry >Specificity in transition state binding: The pauling model revisited
【24h】

Specificity in transition state binding: The pauling model revisited

机译：过渡状态约束力的特异性：重新审视救生模型

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Linus Pauling proposed that the large rate accelerations for enzymes are caused by the high specificity of the protein catalyst for binding the reaction transition state. The observation that stable analogues of the transition states for enzymatic reactions often act as tight-binding inhibitors provided early support for this simple and elegant proposal. We review experimental results that support the proposal that Pauling's model provides a satisfactory explanation for the rate accelerations for many heterolytic enzymatic reactions through high-energy reaction intermediates, such as proton transfer and decarboxylation. Specificity in transition state binding is obtained when the total intrinsic binding energy of the substrate is significantly larger than the binding energy observed at the Michaelis complex. The results of recent studies that aimed to characterize the specificity in binding of the enolate oxygen at the transition state for the 1,3-isomerization reaction catalyzed by ketosteroid isomerase are reviewed. Interactions between pig heart succinyl-coenzyme A:3-oxoacid coenzyme A transferase (SCOT) and the nonreacting portions of coenzyme A (CoA) are responsible for a rate increase of 3 × 10~(12)-fold, which is close to the estimated total 5 × 10~(13)-fold enzymatic rate acceleration. Studies that partition the interactions between SCOT and CoA into their contributing parts are reviewed. Interactions of the protein with the substrate phosphodianion group provide an ～12 kcal/mol stabilization of the transition state for the reactions catalyzed by triosephosphate isomerase, orotidine 5′-monophosphate decarboxylase, and α-glycerol phosphate dehydrogenase. The interactions of these enzymes with the substrate piece phosphite dianion provide a 6-8 kcal/mol stabilization of the transition state for reaction of the appropriate truncated substrate. Enzyme activation by phosphite dianion reflects the higher dianion affinity for binding to the enzyme-transition state complex compared with that of the free enzyme. Evidence is presented that supports a model in which the binding energy of the phosphite dianion piece, or the phosphodianion group of the whole substrate, is utilized to drive an enzyme conformational change from an inactive open form E_O to an active closed form E_C, by closure of a phosphodianion gripper loop. Members of the enolase and haloalkanoic acid dehalogenase superfamilies use variable capping domains to interact with nonreacting portions of the substrate and sequester the substrate from interaction with bulk solvent. Interactions of this capping domain with the phenyl group of mandelate have been shown to activate mandelate racemase for catalysis of deprotonation of α-carbonyl carbon. We propose that an important function of these capping domains is to utilize the binding interactions with nonreacting portions of the substrate to activate the enzyme for catalysis.
机译：Linus Pauling提出了酶的大型速率加速度是由蛋白质催化剂结合反应过渡状态的高特异性引起的。观察到酶促反应的过渡状态稳定类似物通常充当紧密结合抑制剂，为这种简单而优雅的提议提供了早期支持。我们审查了支持鲍林模型通过高能反应中间体的许多异化酶促反应的速率加速度提供了令人满意的解释的实验结果，例如质子转移和脱羧。当基材的总固定能量显着大于在Michaelis络合物中观察到的结合能量时，获得过渡状态结合的特异性。综述旨在表征在由酮酮异构酶催化的1,3-异构化反应的过渡状态下结合烯丙基氧的结合特异性的研究结果进行了研究。猪心脏琥珀酰辅酶A：3-氧代亚胞酶之间的相互作用是转移酶（Scot）和辅酶A（CoA）的非反应部分是率增加3×10〜（12） - 折叠，其接近估计总5×10〜（13） - 粘合酶速率加速。综述了分区苏格兰苏格兰州和COA之间的相互作用的研究得到了审查。蛋白质与基质磷酸二磷酸酯的相互作用提供了通过Triosephosphate异构酶，Orotidine 5'-单磷酸脱羧酶和α-甘油磷酸脱氢酶催化的反应的过渡状态的〜12kcal / mol稳定化。这些酶与基材块亚磷酸酯的相互作用提供6-8kcal / mol稳定的过渡状态，以反应适当的截短的基材。亚磷酸酯的酶活性反映了与游离酶的与酶转变状态复合物结合的较高的脱圆形亲和力。提出了支持亚磷酸酯Dianion片的结合能的模型，或者整个衬底的磷酸二极管基团的模型用于通过闭合驱动从非活动开放形式E_O到主动闭合形式E_C的酶组合变化。磷酸二手夹持器循环。烯醇酶和卤代烷烃的成员脱卤素Superfamilies使用可变封端结构域与基材的非反应部分相互作用，并将基材与配体溶剂相互作用。已经显示出该封端结构域与邦特苯基的相互作用，用于激活牙下的外壳酶，用于催化α-羰基碳的去质子。我们提出这些封端结构域的重要功能是利用与基材的非反应部分的结合相互作用以激活酶的催化。

著录项

  • 来源
    《Biochemistry》 |2013年第12期|共15页
  • 作者

    Amyes T.L.; Richard J.P.;

  • 作者单位

    Department of Chemistry University at Buffalo State University of New York Buffalo NY 14260-3000 United States;

    Department of Chemistry University at Buffalo State University of New York Buffalo NY 14260-3000 United States;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生物化学;
  • 关键词

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号