1c2q
From Proteopedia
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SOLUTION STRUCTURE OF A DNA.RNA HYBRID CONTAINING AN ALPHAT-ANOMERIC THYMIDINE AND POLARITY REVERSALS
Overview
We report the thermodynamic and structural properties of an, alpha-containing DNA.RNA nonamer hybrid duplex, d(ATGG-3'-3'-alphaT-5'-5'-GCTC).r(gagcaccau). The RNA strand corresponds, to the core of the initiation sequence for the transcript of the erbB-2, oncogene. The tandem anomeric and polarity changes in the DNA strand, result in a slight decrease in thermostability (DeltaT(m) = -2.8 degrees, C) compared to the unmodified control hybrid. The three-dimensional, solution structure determination of the alpha-containing DNA.RNA hybrid, conducted via restrained molecular dynamics using interproton distance, (nuclear Overhauser enhancement) and furanose ring torsion angle (J-based), restraints, converged to a final ensemble of structures from unique, starting models. In agreement with hyperchromicity and circular dichroism, data, the final average structure derived from this ensemble is consistent, with an overall A-like motif featuring Watson-Crick base pairing and base, stacking across the entire sequence, albeit with localized B-like traits, within the DNA strand. Comparative pseudorotation analyses of the, J-coupling data for this hybrid and its unmodified control reveal a, surprising increase in S-puckering for two nucleotides immediately, upstream of the 3'-3' linkage, and the associated narrowing of the minor, groove in this portion of the hybrid. Other structural perturbations are, localized to and diagnostic of the central alpha-nucleotide and juxtaposed, polarity reversals. The structural information presented here has direct, relevance to the design of future antisense oligonucleotides composed of, these modifications.
About this Structure
1C2Q is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.
Reference
Solution structure of a DNA.RNA hybrid containing an alpha-anomeric thymidine and polarity reversals: d(ATGG-3'-3'-alphaT-5'-5'-GCTC). r(gagcaccau)., Aramini JM, Germann MW, Biochemistry. 1999 Nov 23;38(47):15448-58. PMID:10569927
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