Basti M M, Stuart J W, Lam A T, Guenther R, Agris P F
Department of Biochemistry, North Carolina State University, Raleigh 27695-7622, USA.
Nat Struct Biol. 1996 Jan;3(1):38-44. doi: 10.1038/nsb0196-38.
Design of biologically active DNA analogues of the yeast tRNA(Phe) anticodon domain, tDNAPheAC, required the introduction of a d(m5C)-dependent, Mg(2+)-induced structural transition and the d(m1G) disruption of an intra-loop dC.dG base pair. The modifications were introduced at residues corresponding to m5C-40 and wybutosine-37 in tRNA(Phe). Modified tDNAPheAC inhibited translation by 50% at a tDNAPheAC: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 A and 1.7 A in the stem, and is similar to the tRNA(Phe) anticodon domain in conformation and dimensions. The tDNAPheAC structure may provide a guide for the design of translation inhibitors as potential therapeutic agents.
