Specificity in transition state binding: the Pauling model revisited.
Specificity in transition state binding: the Pauling model revisited.
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DOI：
10.1021/bi301491r
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发表时间：
2013-03-26
期刊：
影响因子：
2.9
通讯作者：
Richard JP
中科院分区：
文献类型：
--
作者：
Amyes TL;Richard JP
莱纳斯·鲍林提出，酶的大速率加速是由于蛋白质催化剂结合反应过渡态的高度特异性。酶促反应的过渡态的稳定类似物通常作为紧结合抑制剂的观察为这个简单而优雅的提议提供了早期的支持。我们回顾实验结果，支持的建议，Pauling的模型提供了一个令人满意的解释，许多heterolytic酶促反应，通过高能量的反应中间体，如质子转移和脱羧的速率加速。当底物的总固有结合能显著大于在米氏络合物处观察到的结合能时，获得过渡态结合的特异性。综述了近年来甾酮异构酶催化1，3-异构化反应中过渡态烯醇氧结合的特异性研究结果。猪心琥珀酰辅酶A：3-含氧酸辅酶A转移酶（SCOT）与CoA的非反应部分之间的相互作用导致速率增加3 × 1012倍，这接近于估计的总酶促速率加速5 × 1013倍。研究分区SCOT和CoA之间的相互作用到他们的贡献部分进行了审查。蛋白质与底物磷酸二阴离子基团的相互作用提供了一个ca。磷酸丙糖异构酶、乳清酸核苷5′-单磷酸脱羧酶和α-甘油磷酸脱氢酶催化反应过渡态的12 kcal/mol稳定性。这些酶与底物片段亚磷酸根二价阴离子的相互作用为适当的截短底物的反应提供了6 - 8 kcal/mol的过渡态稳定。亚磷酸根二价阴离子对酶的激活作用反映了二价阴离子与酶-过渡态复合物结合的亲和力高于游离酶。证据支持的模型，其中的亚磷酸根二价阴离子片的结合能，或整个基板的phosphodianion组，被用来驱动酶的构象变化从一个非活性的开放形式EO到一个活性的封闭形式EC，通过关闭的phosphodianion夹环。烯醇化酶和卤代烷酸脱卤酶超家族的成员使用可变的加帽结构域与底物的非反应部分相互作用，并隔离底物与本体溶剂的相互作用。已显示该封端结构域与扁桃酸的苯基的相互作用激活扁桃酸消旋酶以催化α-羰基碳的去质子化。我们建议，这些加帽结构域的一个重要功能是利用与底物的非反应部分的结合相互作用来激活酶进行催化。
Linus Pauling proposed that the large rate accelerations for enzymes are due to the high specificity of the protein catalyst for binding the reaction transition state. The observation that stable analogs of the transition states for enzymatic reactions often act as tight-binding binding inhibitors provided early support for this simple and elegant proposal. We review experimental results which 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 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-CoA:3-oxoacid coenzyme A transferase (SCOT) and the nonreacting portions of CoA are responsible for a rate increase of 3 × 1012-fold, which is close to the estimated total 5 × 1013-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 a ca. 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 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 EO to an active closed form EC, 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.
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影响因子：
3.3
作者：
Antoniou, Dimitri;Schwartz, Steven D.
通讯作者：
Schwartz, Steven D.
DOI：
10.1073/pnas.83.11.3743
发表时间：
1986-06-01
影响因子：
11.1
作者：
BRYAN, P;PANTOLIANO, MW;POULOS, T
通讯作者：
POULOS, T
影响因子：
15
作者：
AMYES, TL;RICHARD, JP
通讯作者：
RICHARD, JP
影响因子：
5.6
作者：
Arsenieva, D;Jeffery, CJ
通讯作者：
Jeffery, CJ
DOI：
10.1016/s1570-9639(03)00057-8
发表时间：
2003-04-11
影响因子：
3.2
作者：
Denesyuk, AI;Denessiouk, KA;Johnson, MS
通讯作者：
Johnson, MS