The mechanism of orotidine 5′-monophosphate decarboxylase:: Catalysis by destabilization of the substrate
The mechanism of orotidine 5′-monophosphate decarboxylase:: Catalysis by destabilization of the substrate
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DOI：
10.1021/bi992553w
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发表时间：
2000-02-22
期刊：
影响因子：
2.9
通讯作者：
Wu, WM
中科院分区：
文献类型：
--
作者：
Feng, WY;Austin, TJ;Wu, WM
以乳清酸类似物的脱羧反应为模型体系，研究乳清酸核苷5 '-单磷酸脱羧酶（OMP decarboxylase，ODCase）的作用机理，测定了1，3-二甲基乳清酸及其类似物的脱羧速率和相应碳负离子中间体的稳定性。结果表明，碳负离子中间体的稳定性不是脱羧速率的关键因素。另一方面，反应速率在很大程度上取决于形成两性离子的平衡常数。基于这些结果，我们提出了一种新的机制，其中ODCase通过以两性离子形式结合底物并为OMP的羧酸基团提供不稳定的环境来催化OMP的脱羧。
The mechanism of orotidine 5'-monophosphate decarboxylase (OMP decarboxylase, ODCase) was studied using the decarboxylation of orotic acid analogues as a model system, The rate of decarboxylation of 1,3-dimethylorotic acid and its analogues as well as the stability of their corresponding carbanion intermediates was determined. The results have shown that the stability of the carbanion intermediate is not a critical factor in the rate of decarboxylation. On the other hand, the reaction rate is largely dependent on the equilibrium constant for the formation of a zwitterion. Based on these results, we have proposed a new mechanism in which ODCase catalyzes the decarboxylation of OMP by binding the substrate in a zwitterionic form and providing a destabilizing environment for the carboxylate group of OMP.