1C2Q

SOLUTION STRUCTURE OF A DNA.RNA HYBRID CONTAINING AN ALPHAT-ANOMERIC THYMIDINE AND POLARITY REVERSALS

Summary for 1C2Q

• Entry DOI: 10.2210/pdb1c2q/pdb
• Related: 1BX5
• NMR Information: BMRB: 4547
• Descriptor: 5'-D(ATGG-3'-3'-(T3P)-5'-5'-GCTC)-3', 5'-R(GAGCACCAU)-3' (2 entities in total)
• Functional Keywords: dna/rna hybrid, alphat-anomeric thymidine, 3'-3'/5'-5' phosphodiester linkages, dna-rna hybrid
• Total number of polymer chains: 2
• Total formula weight: 5601.59

Authors

Germann, M.W.,Aramini, J.M. (deposition date: 1999-07-26, release date: 1999-11-29, Last modification date: 2024-05-22)

Primary citation

Aramini, J.M.,Germann, M.W.
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).
Biochemistry, 38:15448-15458, 1999

PubMed Abstract: 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.

PubMed: 10569927
DOI: 10.1021/bi9915418

Experimental method

SOLUTION NMR