THE NUCLEOSIDE DEAMINASES FOR CYTIDINE AND ADENOSINE - STRUCTURE, TRANSITION-STATE STABILIZATION, MECHANISM, AND EVOLUTION
THE NUCLEOSIDE DEAMINASES FOR CYTIDINE AND ADENOSINE - STRUCTURE, TRANSITION-STATE STABILIZATION, MECHANISM, AND EVOLUTION
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DOI：
10.1016/0300-9084(96)88110-7
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发表时间：
1995-01-01
期刊：
影响因子：
3.9
通讯作者：
CARTER, CW
中科院分区：
文献类型：
--
作者：
CARTER, CW
RNA中胞苷和腺苷碱基的酶促脱氨作用最近被证明是改变信使和转运RNA编码特异性的机制。通过X射线晶体学分析了进行相应核苷的脱氨基的酶的结构。它们在许多方面彼此不同，包括四级和三级结构，但它们在活性部位具有相似的化学基团。这两种酶完全包裹它们的核苷底物，这可能是它们对RNA底物无活性的原因。从酶的结构及其与过渡态类似物抑制剂的复合物中，已经了解了很多关于催化机制的知识。催化过程中，结合水分子被锌活化，推测为氢氧根离子，氢氧根离子攻击适当的碳，生成四面体中间体。所得两个手性中心的详细立体化学为非对映异构体。随后产生和释放产物所需的质子转移步骤的细节在两种酶中也明显不同。因此，活性位点的相似性可能是趋同进化的结果。
Enzymatic deamination of cytidine and adenosine bases in RNA have recently been shown to be mechanisms for changing the coding specificity of messenger and transfer RNAs. The structures of the enzymes that carry out deamination of the corresponding nucleosides have been analyzed by X-ray crystallography. They are quite different from one another in most respects, including quaternary and tertiary structure, but they have similar chemical groups in their active sites. Both enzymes envelope their nucleoside substrates completely, perhaps accounting for the fact that they are inactive on RNA substrates. Much has been learned about catalytic mechanisms from the structures of the enzymes and their complexes with transition state analog inhibitors. Catalysis proceeds with the activation by zinc of a bound water molecule, presumably to hydroxide ion, which attacks the appropriate carbon to generate a tetrahedral intermediate. The detailed stereochemistry of the two resulting chiral centers is diastereoisomeric. Details of the ensuing proton transfer steps necessary to generate and release the products are also apparently different in the two enzymes. Thus, the active site similarities are probably the result of convergent evolution.