Design, biological activity and NMR-solution structure of a DNA analogue of yeast tRNAPhe anticodon domain

Design of biologically active DNA analogues of the yeast tRNA Phe anticodon domain, tDNA Phe AC , required the introduction of a d(m 5 C)-dependent, Mg 2+ -induced structural transition and the d(m 1 G) disruption of an intra-loop dC·dG base pair. The modifications were introduced at residues corres...

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Veröffentlicht in:Nature Structural Biology 1996-01, Vol.3 (1), p.38-44
Hauptverfasser: Basti, M.M., Stuart, J.W., Lam, A.T., Guenther, R., Agris, P.F.
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Sprache:eng
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Zusammenfassung:Design of biologically active DNA analogues of the yeast tRNA Phe anticodon domain, tDNA Phe AC , required the introduction of a d(m 5 C)-dependent, Mg 2+ -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 Phe AC inhibited translation by 50% at a tDNA Phe AC :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 Å and 1.7 Å in the stem, and is similar to the tRNA Phe anticodon domain in conformation and dimensions. The tDNA Phe AC structure may provide a guide for the design of translation inhibitors as potential therapeutic agents.
ISSN:1072-8368
1545-9985
DOI:10.1038/nsb0196-38