Takagi Y, Warashina M, Stec W J, Yoshinari K, Taira K
Gene Discovery Research Center, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba Science City 305-8562, Japan.
Nucleic Acids Res. 2001 May 1;29(9):1815-34. doi: 10.1093/nar/29.9.1815.
The cleavage of RNA can be accelerated by a number of factors. These factors include an acidic group (Lewis acid) or a basic group that aids in the deprotonation of the attacking nucleophile, in effect enhancing the nucleophilicity of the nucleophile; an acidic group that can neutralize and stabilize the leaving group; and any environment that can stabilize the pentavalent species that is either a transition state or a short-lived intermediate. The catalytic properties of ribozymes are due to factors that are derived from the complicated and specific structure of the ribozyme-substrate complex. It was postulated initially that nature had adopted a rather narrowly defined mechanism for the cleavage of RNA. However, recent findings have clearly demonstrated the diversity of the mechanisms of ribozyme-catalyzed reactions. Such mechanisms include the metal-independent cleavage that occurs in reactions catalyzed by hairpin ribozymes and the general double-metal-ion mechanism of catalysis in reactions catalyzed by the Tetrahymena group I ribozyme. Furthermore, the architecture of the complex between the substrate and the hepatitis delta virus ribozyme allows perturbation of the pK(a) of ring nitrogens of cytosine and adenine. The resultant perturbed ring nitrogens appear to be directly involved in acid/base catalysis. Moreover, while high concentrations of monovalent metal ions or polyamines can facilitate cleavage by hammerhead ribozymes, divalent metal ions are the most effective acid/base catalysts under physiological conditions.
RNA的切割可被多种因素加速。这些因素包括一个酸性基团（路易斯酸）或一个有助于进攻性亲核试剂去质子化的碱性基团，实际上增强了亲核试剂的亲核性；一个能够中和并稳定离去基团的酸性基团；以及任何能够稳定作为过渡态或短寿命中间体的五价物种的环境。核酶的催化特性归因于源自核酶-底物复合物复杂且特定结构的因素。最初推测自然界采用了一种相当狭义定义的RNA切割机制。然而，最近的研究结果清楚地证明了核酶催化反应机制的多样性。此类机制包括发夹状核酶催化反应中发生的不依赖金属的切割以及嗜热四膜虫I型核酶催化反应中的一般双金属离子催化机制。此外，底物与丁型肝炎病毒核酶之间复合物的结构允许对胞嘧啶和腺嘌呤环氮原子的pK(a)进行扰动。由此产生的被扰动的环氮原子似乎直接参与酸碱催化。而且，虽然高浓度的单价金属离子或多胺可促进锤头状核酶的切割，但在生理条件下二价金属离子是最有效的酸碱催化剂。
