1d7z

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(New page: 200px<br /><applet load="1d7z" size="450" color="white" frame="true" align="right" spinBox="true" caption="1d7z, resolution 2.21&Aring;" /> '''CRYSTAL STRUCTURE OF...)
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[[Image:1d7z.gif|left|200px]]<br /><applet load="1d7z" size="350" color="white" frame="true" align="right" spinBox="true"
caption="1d7z, resolution 2.21&Aring;" />
caption="1d7z, resolution 2.21&Aring;" />
'''CRYSTAL STRUCTURE OF A HEXITOL NUCLEIC ACID (HNA) DUPLEX AT 2.2 A RESOLUTION'''<br />
'''CRYSTAL STRUCTURE OF A HEXITOL NUCLEIC ACID (HNA) DUPLEX AT 2.2 A RESOLUTION'''<br />
==Overview==
==Overview==
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A huge variety of chemically modified oligonucleotide derivatives has been, synthesized for possible antisense applications. One such derivative, hexitol nucleic acid (HNA), is a DNA analogue containing the standard, nucleoside bases, but with a phosphorylated 1',5'-anhydrohexitol backbone., Hexitol nucleic acids are some of the strongest hybridizing antisense, compounds presently known, but HNA duplexes are even more stable. We, present here the first high-resolution structure of a double helical, nucleic acid with all sugars being hexitols. Although designed to have a, restricted conformational flexibility, the hexitol oligomer h(GTGTACAC) is, able to crystallize in two different double helical conformations. Both, structures display a high x-displacement, normal Watson-Crick base, pairing, similar base stacking patterns, and a very deep major groove, together with a minor groove with increased hydrophobicity. One of the, conformations displays a major groove which is wide enough to accommodate, a second HNA double helix resulting in the formation of a double helix of, HNA double helices. Both structures show most similarities with the A-type, helical structure, the anhydrohexitol chair conformation thereby acting as, a good mimic for the furanose C3'-endo conformation observed in RNA. As, compared to the quasi-linear structure of homo-DNA, the axial position of, the base in HNA allows efficient base stacking and hence double helix, formation.
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A huge variety of chemically modified oligonucleotide derivatives has been synthesized for possible antisense applications. One such derivative, hexitol nucleic acid (HNA), is a DNA analogue containing the standard nucleoside bases, but with a phosphorylated 1',5'-anhydrohexitol backbone. Hexitol nucleic acids are some of the strongest hybridizing antisense compounds presently known, but HNA duplexes are even more stable. We present here the first high-resolution structure of a double helical nucleic acid with all sugars being hexitols. Although designed to have a restricted conformational flexibility, the hexitol oligomer h(GTGTACAC) is able to crystallize in two different double helical conformations. Both structures display a high x-displacement, normal Watson-Crick base pairing, similar base stacking patterns, and a very deep major groove together with a minor groove with increased hydrophobicity. One of the conformations displays a major groove which is wide enough to accommodate a second HNA double helix resulting in the formation of a double helix of HNA double helices. Both structures show most similarities with the A-type helical structure, the anhydrohexitol chair conformation thereby acting as a good mimic for the furanose C3'-endo conformation observed in RNA. As compared to the quasi-linear structure of homo-DNA, the axial position of the base in HNA allows efficient base stacking and hence double helix formation.
==About this Structure==
==About this Structure==
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1D7Z 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1D7Z OCA].
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1D7Z 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=1D7Z OCA].
==Reference==
==Reference==
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[[Category: Protein complex]]
[[Category: Protein complex]]
[[Category: Declercq, R.]]
[[Category: Declercq, R.]]
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[[Category: Meervelt, L.Van.]]
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[[Category: Meervelt, L Van.]]
[[Category: dna analogue]]
[[Category: dna analogue]]
[[Category: double helix]]
[[Category: double helix]]
[[Category: hexitol nucleic acid]]
[[Category: hexitol nucleic acid]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sun Nov 25 02:41:58 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:13:55 2008''

Revision as of 10:13, 21 February 2008


1d7z, resolution 2.21Å

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CRYSTAL STRUCTURE OF A HEXITOL NUCLEIC ACID (HNA) DUPLEX AT 2.2 A RESOLUTION

Overview

A huge variety of chemically modified oligonucleotide derivatives has been synthesized for possible antisense applications. One such derivative, hexitol nucleic acid (HNA), is a DNA analogue containing the standard nucleoside bases, but with a phosphorylated 1',5'-anhydrohexitol backbone. Hexitol nucleic acids are some of the strongest hybridizing antisense compounds presently known, but HNA duplexes are even more stable. We present here the first high-resolution structure of a double helical nucleic acid with all sugars being hexitols. Although designed to have a restricted conformational flexibility, the hexitol oligomer h(GTGTACAC) is able to crystallize in two different double helical conformations. Both structures display a high x-displacement, normal Watson-Crick base pairing, similar base stacking patterns, and a very deep major groove together with a minor groove with increased hydrophobicity. One of the conformations displays a major groove which is wide enough to accommodate a second HNA double helix resulting in the formation of a double helix of HNA double helices. Both structures show most similarities with the A-type helical structure, the anhydrohexitol chair conformation thereby acting as a good mimic for the furanose C3'-endo conformation observed in RNA. As compared to the quasi-linear structure of homo-DNA, the axial position of the base in HNA allows efficient base stacking and hence double helix formation.

About this Structure

1D7Z is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.

Reference

Crystal structure of double helical hexitol nucleic acids., Declercq R, Van Aerschot A, Read RJ, Herdewijn P, Van Meervelt L, J Am Chem Soc. 2002 Feb 13;124(6):928-33. PMID:11829600

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