1l0r
From Proteopedia
(New page: 200px<br /><applet load="1l0r" size="450" color="white" frame="true" align="right" spinBox="true" caption="1l0r" /> '''NMR Solution Structure of Nogalamycin Interc...) |
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'''NMR Solution Structure of Nogalamycin Intercalation Between Co-Axially Stacked Hairpins'''<br /> | '''NMR Solution Structure of Nogalamycin Intercalation Between Co-Axially Stacked Hairpins'''<br /> | ||
==Overview== | ==Overview== | ||
- | Two DNA hairpin motifs (5'-GCGAAGC-3' and 5'-ACGA AGT-3'), both stabilized | + | Two DNA hairpin motifs (5'-GCGAAGC-3' and 5'-ACGA AGT-3'), both stabilized by a 5'-GAA loop, have been used to design novel intramolecular double hairpin structures (5'-GCGAAGCACGAAGT-3' and 5'-ACGAAGTGCG AAGC-3') in which coaxial stacking of the two hairpin components generates a double-stranded stem region effectively with a single-strand break in the middle of the sequence at either the TG or CA step between unconnected 3' and 5' terminal bases. We have investigated by NMR the conformation and dynamics of the DNA at the strand break site. We show that mutual stacking significantly enhances the stability of each hairpin. Further, the anthracycline antibiotic nogalamycin binds cleanly to the 5'-TG (5'-CA) site formed by the mutually stacked hairpins despite the break in the sugar-phosphate backbone on one strand. The complex resembles the structure of nogalamycin-DNA complexes with the drug bound at 5'-TG sites in intact duplex sequences, with pi-stacking interactions probably the single dominant stabilizing interaction. |
==About this Structure== | ==About this Structure== | ||
- | 1L0R is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with NA and NGP as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1L0R is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=NA:'>NA</scene> and <scene name='pdbligand=NGP:'>NGP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1L0R OCA]. |
==Reference== | ==Reference== | ||
Drug recognition of a DNA single strand break: nogalamycin intercalation between coaxially stacked hairpins., Williams HE, Colgrave ML, Searle MS, Eur J Biochem. 2002 Mar;269(6):1726-33. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11895443 11895443] | Drug recognition of a DNA single strand break: nogalamycin intercalation between coaxially stacked hairpins., Williams HE, Colgrave ML, Searle MS, Eur J Biochem. 2002 Mar;269(6):1726-33. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11895443 11895443] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
- | [[Category: Colgrave, M | + | [[Category: Colgrave, M L.]] |
- | [[Category: Searle, M | + | [[Category: Searle, M S.]] |
- | [[Category: Williams, H | + | [[Category: Williams, H E.L.]] |
[[Category: NA]] | [[Category: NA]] | ||
[[Category: NGP]] | [[Category: NGP]] | ||
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[[Category: single strand break]] | [[Category: single strand break]] | ||
- | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:40:07 2008'' |
Revision as of 11:40, 21 February 2008
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NMR Solution Structure of Nogalamycin Intercalation Between Co-Axially Stacked Hairpins
Overview
Two DNA hairpin motifs (5'-GCGAAGC-3' and 5'-ACGA AGT-3'), both stabilized by a 5'-GAA loop, have been used to design novel intramolecular double hairpin structures (5'-GCGAAGCACGAAGT-3' and 5'-ACGAAGTGCG AAGC-3') in which coaxial stacking of the two hairpin components generates a double-stranded stem region effectively with a single-strand break in the middle of the sequence at either the TG or CA step between unconnected 3' and 5' terminal bases. We have investigated by NMR the conformation and dynamics of the DNA at the strand break site. We show that mutual stacking significantly enhances the stability of each hairpin. Further, the anthracycline antibiotic nogalamycin binds cleanly to the 5'-TG (5'-CA) site formed by the mutually stacked hairpins despite the break in the sugar-phosphate backbone on one strand. The complex resembles the structure of nogalamycin-DNA complexes with the drug bound at 5'-TG sites in intact duplex sequences, with pi-stacking interactions probably the single dominant stabilizing interaction.
About this Structure
1L0R is a Protein complex structure of sequences from [1] with and as ligands. Full crystallographic information is available from OCA.
Reference
Drug recognition of a DNA single strand break: nogalamycin intercalation between coaxially stacked hairpins., Williams HE, Colgrave ML, Searle MS, Eur J Biochem. 2002 Mar;269(6):1726-33. PMID:11895443
Page seeded by OCA on Thu Feb 21 13:40:07 2008