Design, biological activity and NMR-solution structure of a DNA analogue of yeast tRNA(Phe) anticodon domain

被引：28

作者：

Basti, MM ^{[1
]}

Stuart, JW ^{[1
]}

Lam, AT ^{[1
]}

Guenther, R ^{[1
]}

Agris, PF ^{[1
]}

机构：

[1] N CAROLINA STATE UNIV,DEPT BIOCHEM,RALEIGH,NC 27695

来源：

NATURE STRUCTURAL BIOLOGY | 1996年 / 3卷 / 01期

关键词：

D O I：

10.1038/nsb0196-38

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：38 / 44

页数：7

共 41 条

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