1c2q: Difference between revisions
New page: left|200px<br /><applet load="1c2q" size="450" color="white" frame="true" align="right" spinBox="true" caption="1c2q" /> '''SOLUTION STRUCTURE OF A DNA.RNA HYBRID CONTA... |
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[[Image:1c2q.gif|left|200px]]<br /><applet load="1c2q" size=" | [[Image:1c2q.gif|left|200px]]<br /><applet load="1c2q" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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'''SOLUTION STRUCTURE OF A DNA.RNA HYBRID CONTAINING AN ALPHAT-ANOMERIC THYMIDINE AND POLARITY REVERSALS'''<br /> | '''SOLUTION STRUCTURE OF A DNA.RNA HYBRID CONTAINING AN ALPHAT-ANOMERIC THYMIDINE AND POLARITY REVERSALS'''<br /> | ||
==Overview== | ==Overview== | ||
We report the thermodynamic and structural properties of an | 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== | ==About this Structure== | ||
1C2Q is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http:// | 1C2Q is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1C2Q OCA]. | ||
==Reference== | ==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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10569927 10569927] | 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10569927 10569927] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Aramini, J | [[Category: Aramini, J M.]] | ||
[[Category: Germann, M | [[Category: Germann, M W.]] | ||
[[Category: 3'-3'/5'-5' phosphodiester linkages]] | [[Category: 3'-3'/5'-5' phosphodiester linkages]] | ||
[[Category: alphat-anomeric thymidine]] | [[Category: alphat-anomeric thymidine]] | ||
[[Category: dna/rna hybrid]] | [[Category: dna/rna hybrid]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:01:47 2008'' | ||
Revision as of 10:01, 21 February 2008
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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
Page seeded by OCA on Thu Feb 21 12:01:47 2008
