RECOGNITION AND CATALYSIS IN NUCLEIC-ACID CHEMISTRY
RECOGNITION AND CATALYSIS IN NUCLEIC-ACID CHEMISTRY
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DOI：
10.1073/pnas.90.4.1201
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发表时间：
1993-02-15
影响因子：
11.1
通讯作者：
XU, R
中科院分区：
文献类型：
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作者：
BRESLOW, R;XU, R
核糖核酸酶A以组氨酸-12和组氨酸-119的咪唑基团为主要催化基团，催化RNA的裂解。模型研究表明，RNA可以被咪唑缓冲液本身切割，并且，正如在酶中一样，可以看到一个钟形的pH与速率曲线。这表明一种咪唑作为碱，而另一种作为咪唑离子作为酸。然而，与酶的情况相反，简单模型使用咪唑在顺序，而不是同时，双功能催化。对该反应的机理研究以及咪唑和其他缓冲剂催化的简单二核苷酸反应确定了该过程的细节。这些结果让我们提出了一种不同于标准的酶促过程机制；他们还鼓励我们设计一种改良的酶的模拟物，使用类似于酶的机制。机制研究的关键是观察正常的3',5 “ RNA核苷酸到2',5 ”异构体的重排。这使我们研究了DNA同分异构体的性质，其中一个2',5 “的链接也取代了正常的3',5 ”的链接。结果表明，双螺旋结构的碱基堆叠较差，使其不适合作为遗传单位。
The enzyme ribonuclease A catalyzes the cleavage of RNA, using the imidazole groups of histidine-12 and histidine-119 as its principal catalytic groups. Model studies show that RNA can be cleaved by imidazole buffer itself and that, as in the enzyme, a bell-shaped pH vs. rate profile is seen. This indicates that one imidazole functions as a base, while the other, as the imidazolium ion, functions as an acid. However, in contrast to the enzymatic case, the simple model uses the imidazoles in sequential, rather than simultaneous, bifunctional catalysis. Mechanistic studies on this reaction and on the reactions of simple dinucleotides catalyzed by imidazole and other buffers establish the details of the process. The results let us propose a mechanism for the enzymatic process different from the standard one; they also stimulated us to design an improved mimic of the enzyme that uses a mechanism like that proposed for the enzyme. Critical to the mechanistic studies is observation of the rearrangement of normal 3',5'' RNA nucleotides to the 2',5'' isomers. This led us to investigate the properties of DNA isomers in which a 2',5'' link also replaces the normal 3',5'' one. The results indicate that poor base stacking in a double helix with such links makes them less suitable as genetic units.