Redesign of an artificial ligase ribozyme based on the analysis of its structural elements.
Redesign of an artificial ligase ribozyme based on the analysis of its structural elements.
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DOI：
10.4161/rna.2.4.2302
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发表时间：
2005-10-01
期刊：
影响因子：
4.1
通讯作者：
Inoue, Tan
中科院分区：
文献类型：
--
作者：
Ikawa, Yoshiya;Matsumoto, Junko;Inoue, Tan
研究了“DSL核酶”的催化和折叠性能。这种人工连接酶核酶是通过在设计的自折叠RNA上安装催化单元来构建的。自折叠RNA由三个螺旋组成，通过两个三级相互作用连接，在分子设计中充当支架。目前的分析表明，GAAA环与其特异性受体之间的三级相互作用在活性结构的折叠和催化位点的精确定位中起着至关重要的作用。在分析的基础上，核酶被重新设计并转化为两种高级形式--具有明显催化活性的较小的衍生物和具有RNA聚合酶活性的衍生物。这项研究表明，如果人工核酶的结构元素得到很好的解析，那么重新设计它是有效和高效的。这种分子转化可以作为理解自然产生的核酶分子组织和进化的原型模型。
The catalytic and folding properties of "DSL ribozyme" were investigated. This artificial ligase ribozyme was constructed by installing a catalytic unit to a designed self-folding RNA. The self-folding RNA was composed of three helices connected via two tertiary interactions that served as scaffolding in the molecular design. The present analysis revealed that the tertiary interaction between the GAAA loop and its specific receptor plays a crucial role in the folding of the active structure and the precise positioning of the catalytic site. On the basis of the analyses, the ribozyme was redesigned and converted to two advanced forms--a smaller derivative with appreciable catalytic activity and a derivative with RNA polymerase-like activity. The study demonstrates that redesign of an artificial ribozyme is effective and efficient if its structural elements are finely resolved. This kind of molecular transformation should serve as a prototypic model for understanding the molecular organization and evolution of naturally occurring ribozymes.