Enzymes work by solvation substitution rather than by desolvation.
Enzymes work by solvation substitution rather than by desolvation.
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酶通过溶剂化取代而不是去溶剂化起作用。
DOI：
10.1073/pnas.86.15.5820
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发表时间：
1989
影响因子：
11.1
通讯作者：
Creighton,S
中科院分区：
文献类型：
--
作者：
Warshel,A;Aqvist,J;Creighton,S
最近，酶通过置换溶剂并为反应底物创造类似于气相的环境来催化其反应的假设引起了相当大的关注。本文通过定义不同环境下反应的共同参考能量，重新审视了这一“去溶剂化假说”。有人认为，一致的尝试来描述酶促反应的实际能量学，无论是气相或溶液作为参考，将与上述假设相矛盾。也就是说，酶确实从其底物中去除了水分子，但将这些分子替换为另一个极性环境（即其活性位点）。以酰胺水解为例，我们使用实验估计的溶剂化能和分析的反应曲线在气相中，在溶液中，和在酶的活性位点。我们表明，气相反应的特点是由一个巨大的活化势垒（与形成带电的亲核试剂从中性片段），虽然亲核攻击基本上是无势垒的。另一方面，发现酶和溶液反应具有相似的反应曲线，酶促反应具有较低的活化势垒。据推测，事实上，以前的分析这个问题并没有涉及相关的热力学循环的建设（和相应的溶剂化能量的定量估计）导致去溶剂化假说。我们的结论是，酶的活性位点提供特定的极性环境，不类似于气相，但被设计为静电稳定的离子过渡态和“溶剂化”这些状态比水。
Considerable attention has recently been drawn to the hypothesis that enzymes catalyze their reactions by displacing solvent and creating an environment similar to the gas phase for the reacting substrates. This "desolvation hypothesis" is reexamined in this paper by defining a common reference energy for reactions in various environments. It is argued that consistent attempts to describe the actual energetics of enzymatic reactions, taking either gas phase or solution as a reference, would contradict the above hypothesis. That is, the enzyme does remove water molecules from its substrate, but substitutes these molecules for another polar environment (namely, its active site). By taking amide hydrolysis as an example, we use experimentally estimated solvation energies and analyze the reaction profile in the gas phase, in solution, and in enzyme active sites. We show that the gas-phase reaction is characterized by an enormous activation barrier (associated with forming the charged nucleophile from neutral fragments), although the nucleophilic attack is essentially barrierless. On the other hand, the enzyme and solution reactions are found to have similar reaction profiles, with a lower activation barrier for the enzymatic reaction. Presumably, the fact that previous analyses of this problem did not involve the construction of the relevant thermodynamic cycles (and quantitative estimates of the corresponding solvation energies) led to the desolvation hypothesis. Our conclusion is that enzyme active sites provide specific polar environments that do not resemble the gas phase but that are designed for electrostatic stabilization of ionic transition states and that "solvate" these states more than water does.