Design, biological activity and NMR-solution structure of a DNA analogue of yeast tRNA(Phe) anticodon domain
Design, biological activity and NMR-solution structure of a DNA analogue of yeast tRNA(Phe) anticodon domain
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DOI：
10.1038/nsb0196-38
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发表时间：
1996-01-01
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影响因子：
--
通讯作者：
Agris, PF
中科院分区：
文献类型：
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作者：
Basti, MM;Stuart, JW;Agris, PF
酵母tRNA(Phe)反密码子结构域的生物活性DNA类似物tDNA(AC)(Phe)的设计需要引入d(m(5)C)依赖的、由镁离子诱导的结构转变和环内DC的d(m(1)G)中断。DG碱基对。这些修饰是在tRNA(Phe)中对应于m(5)C-40和wybuosine-37的残基引入的。当tDNA(AC)(Phe)与核糖体的比例为8：1时，经修饰的tDNA(AC)(Phe)可抑制50%的翻译。用核磁共振波谱和抑制分子动力学方法确定了该分子的结构。在茎中分别为2.8 Angstrom和1.7 Angstrom，在构象和尺寸上与tRNA(Phe)反密码子结构域相似。TDNA(AC)(Phe)结构可能为翻译抑制剂作为潜在的治疗药物的设计提供指导。
Design of biologically active DNA analogues of the yeast tRNA(Phe) anticodon domain, tDNA(AC)(Phe), required the introduction of a d(m(5)C)-dependent, Mg2+-induced structural transition and the d(m(1)G) disruption of an intra-loop dC . dG base pair. The modifications were introduced at residues corresponding to m(5)C-40 and wybutosine-37 in tRNA(Phe). Modified tDNA(AC)(Phe) inhibited translation by 50% at a tDNA(AC)(Phe):ribosome ratio of 8:1. The molecule's structure has been determined by NMR spectroscopy and restrained molecular dynamics with an overall r.m.s.d. of 2.8 Angstrom and 1.7 Angstrom in the stem, and is similar to the tRNA(Phe) anticodon domain in conformation and dimensions. The tDNA(AC)(Phe) structure may provide a guide for the design of translation inhibitors as potential therapeutic agents.