Rational optimization of the DSL ligase ribozyme with GNRA/receptor interacting modules
Rational optimization of the DSL ligase ribozyme with GNRA/receptor interacting modules
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DOI：
10.1016/j.abb.2009.08.020
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发表时间：
2009-10-15
影响因子：
3.9
通讯作者：
Ikawa, Yoshiya
中科院分区：
文献类型：
--
作者：
Ishikawa, Junya;Matsumura, Shigeyoshi;Ikawa, Yoshiya
DSL核酶是一类具有高度模块化结构的人工连接酶核酶，其催化螺旋底物模块上的模板指导的RNA连接，所述螺旋底物模块可以与催化模块共价连接（顺式DSL）或物理分离（反式DSL）。通过催化模块的底物识别分别通过一组或两组在顺式或反式构型中充当夹的GNRA/受体相互作用来促进。在这项研究中，我们已经合理地设计和分析了几个trans-DSL核酶的催化和自组装性能与不同的天然和人工GNRA受体夹。在这项研究中新设计的两个变体显示出显着增强的催化性能与原来的trans-DSL构建。虽然这项工作允许解剖的trans-DSL核酶的营业额和催化性能，它也强调了显着的模块化的RNA三级结构的纳米结构的复杂功能。(C)2009 Elsevier Inc. All rights reserved.
The DSL ribozyme is a class of artificial ligase ribozymes with a highly modular architecture, which catalyzes template-directed RNA ligation on a helical substrate module that can be either covalently connected (cis-DSL) or physically separated (trans-DSL) from the catalytic module. Substrate recognition by the catalytic module is promoted by one or two sets of GNRA/receptor interactions acting as clamps in the cis or trans configurations, respectively. In this study, we have rationally designed and analyzed the catalytic and self-assembly properties of several trans-DSL ribozymes with different sets of natural and artificial GNRA-receptor clamps. Two variants newly designed in this study showed significantly enhanced catalytic properties with respect of the original trans-DSL construct. While this work allows dissection of the turnover and catalytic properties of the trans-DSL ribozyme, it also emphasizes the remarkable modularity of RNA tertiary structure for nano-construction of complex functions. (C) 2009 Elsevier Inc. All rights reserved.