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PDBsum entry 1ac3
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DNA-RNA hybrid
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PDB id
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1ac3
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References listed in PDB file
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Key reference
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Title
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Solution structure of an RNA X DNA hybrid duplex containing a 3'-Thioformacetal linker and an RNA a-Tract.
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Authors
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C.W.Cross,
J.S.Rice,
X.Gao.
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Ref.
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Biochemistry, 1997,
36,
4096-4107.
[DOI no: ]
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PubMed id
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Abstract
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Neutral and achiral backbone linkers are promising replacements for the
phosphodiester linkages of antisense oligonucleotides that target mRNA
sequences. Results are presented here for the solution structure elucidation by
NMR of an RNA x DNA hybrid duplex, r(GCGCAAAACGCG) x d(CGCGTT-SCH2O-TTGCGC)
(designated RIII), containing a 3'-thioformacetal (3'-TFMA) backbone
substitution in the DNA strand. The 3'-thioformacetal linker can be accommodated
in the hybrid duplex in a conformation that is drastically different from its
form in a DNA x DNA duplex but close to that of the canonical A-form helix,
reflecting the sequence requirement for hybridization. While the global features
of RIII are similar to what are described in the literature, the 3'-TFMA
modification drives sugar puckers of the adjacent residues to more C3'-endo-like
conformations and causes distortions in related twist angles and helical rises.
The helical conformation analyses of each of the two strands and the hybrid
duplex enable a clear account of the conformational variability of both the DNA
and RNA strands. The A-tract in the RNA strand features an overall straight
helix and a more prominent bend at the 3'-end CG step. The structure of RIII
provides a structural basis for the improved thermal stability of RIII compared
to the corresponding DNA x DNA duplex and insights into the factors that are
important concerns for the design of new, effective antisense oligonucleotides.
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Headers
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