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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Exceptionally fast self-cleavage by a Neurospora Varkud satellite ribozyme
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Exceptionally fast self-cleavage by a Neurospora Varkud satellite ribozyme

机译:Neurospora Varkud卫星核酶异常快速的自我切割

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摘要

Most of the small ribozymes, including those that have been investigated as potential therapeutic agents, appear to be rather poor catalysts. These RNAs use an internal phosphoester transfer mechanism to catalyze site-specific RNA cleavage with apparent cleavage rate constants typically <2 min~(-1). We have identified variants of one of these, the Neurospora Varkud satellite ribozyme, that self-cleaves with experimentally measured apparent rate constants of up to 10 s~(-1) (500 min~(-1)), ≈2 orders of magnitude faster than any previously characterized self-cleaving RNA. We describe structural features of the cleavage site loop and an adjacent helix that affect the apparent rate constants for cleavage and ligation and the equilibrium between them. These data show that the phosphoester transfer ribozymes can catalyze reactions with rate constants much larger than previously appreciated and in the range of those of protein enzymes that perform similar reactions.
机译:大多数小的核酶,包括已被研究为潜在治疗剂的那些,似乎都是较差的催化剂。这些RNA使用内部磷酸酯转移机制来催化位点特异性RNA裂解,其表观裂解速率常数通常<2 min〜(-1)。我们已经确定了其中一种变体,即神经孢子变种卫星核酶,可以通过实验测得的表观速率常数高达10 s〜(-1)(500 min〜(-1))自爆,≈2个数量级比任何先前表征的自切割RNA更快。我们描述了裂解位点环和相邻螺旋的结构特征,这些结构特征影响裂解和连接的表观速率常数以及它们之间的平衡。这些数据表明,磷酸酯转移核酶可以催化反应,其速率常数比以前认为的大得多,并且在进行类似反应的蛋白质酶的范围内。

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