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首页> 外文期刊>Biochemistry >A core folding model for catalysis by the hammerhead ribozyme accounts for its extraordinary sensitivity to abasic mutations [Review]
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A core folding model for catalysis by the hammerhead ribozyme accounts for its extraordinary sensitivity to abasic mutations [Review]

机译：锤头状核酶催化的核心折叠模型说明了其对无碱基突变的非凡敏感性[综述]

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摘要

Introducing abasic nucleotides at each of 13 positions in the conserved core of the hammerhead ribozyme causes a large decrease in the extent of catalysis [Peracchi, A., et al. (1996) Proc. Natl. Acad. Sci. U.S.A. 93, 11522]. This extreme sensitivity to structural defects is in contrast to the behavior of protein enzymes and larger ribozymes. Several additional differences in the behavior of the hammerhead relative to that of protein enzymes and larger ribozymes are described herein. The deleterious effects of the abasic mutations are not relieved by lowering the temperature, by increasing the concentration of monovalent or divalent metal ions, or by adding polyamines, in contrast to effects observed with protein enzymes and large RNA enzymes. In addition, the abasic mutations do not significantly weaken substrate binding. These results and previous observations are all; accounted for by a "core folding" model in which the stable ground state structure of the hammerhead ribozyme complexed with the substrate is a partially folded state that must undergo an additional folding event to achieve its catalytic conformation. We propose that the peculiar behavior of the hammerhead arises because the limited structural interconnections in a small RNA enzyme do not allow the ground state to stably adopt the catalytic conformation; within the globally folded catalytic conformation, limited structural interconnections may further impair catalysis by hampering the precise alignment of active site functional groups. This behavior represents a basic manifestation of the well-recognized interconnection between folding and catalysis. [References: 129]
机译：在锤头状核酶保守核的13个位置的每一个位置引入无碱基核苷酸会导致催化程度的大幅度降低[Peracchi，A。等人。 （1996）美国国家科学院院刊。 Natl。学院科学美国，第93卷，第11522页]。这种对结构缺陷的极端敏感性与蛋白质酶和较大的核酶的行为相反。相对于蛋白质酶和较大的核酶而言，锤头的行为还存在一些其他差异。与通过蛋白质酶和大RNA酶观察到的效果相反，通过降低温度，通过增加单价或二价金属离子的浓度或通过添加多胺不能减轻无碱基突变的有害作用。此外，无碱基突变不会显着削弱底物结合。这些结果和以前的观察都是全部;由“核心折叠”模型解释，其中与基质复合的锤头状核酶的稳定基态结构是部分折叠状态，必须经历额外的折叠事件才能实现其催化构象。我们提出锤头的特殊行为是由于小RNA酶中有限的结构互连不允许基态稳定地采用催化构象而引起的。在全局折叠的催化构象内，有限的结构互连可能会通过阻碍活性位点官能团的精确排列而进一步削弱催化作用。这种行为代表了折叠和催化之间公认的相互联系的基本表现。 [参考：129]

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