Catalysis by enzyme conformational change as illustrated by orotidine 5′-monophosphate decarboxylase
Catalysis by enzyme conformational change as illustrated by orotidine 5′-monophosphate decarboxylase
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DOI：
10.1016/s0959-440x(03)00041-1
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发表时间：
2003-04-01
影响因子：
6.8
通讯作者：
Gao, JL
中科院分区：
文献类型：
--
作者：
Gao, JL
用能量分解方案阐明了酶构象亚态的变化对酶催化反应中活性势垒降低的重要性。这一分析可以通过5‘-单磷酸核苷脱羧酶的反应来说明，与非催化过程相比，其反应速度显著提高了17个数量级以上。反应机理表明，酶在反应态的构象比在过渡态的构象更扭曲。蛋白质构象松弛释放的能量为5-单磷酸脱羧酶的速率提高提供了主要的贡献。所提出的机制与定点突变实验的结果是一致的，在该实验中，远离反应中心的突变可以对催化速率增强(k(CAT))产生显著影响，但对与底物的结合亲和力(K-M)的影响较小。
An energy decomposition scheme has been used to elucidate the importance of the changes of enzyme conformational substates to the reduction of the activation barrier in enzyme-catalyzed reactions. This analysis may be illustrated by the reaction of orotidine 5'-monophosphate decarboxylase, which exhibits a remarkable rate enhancement of over 17 orders of magnitude compared to the uncatalyzed process. The mechanism shows that the enzyme conformation is more distorted in the reactant state than in the transition state. The energy released from protein conformation relaxation provides the predominant contribution to the rate enhancement of orotidine 5-monophosphate decarboxylase. The proposed mechanism is consistent with results from site-directed mutagenesis experiments, in which mutations distant from the reactive center can have significant effects on the catalytic rate enhancement (k(cat)), but rather a small influence on the binding affinity for the substrate (K-M).