481d
From Proteopedia
(New page: 200px<br /><applet load="481d" size="350" color="white" frame="true" align="right" spinBox="true" caption="481d, resolution 1.60Å" /> '''CRYSTAL STRUCTURE OF...) |
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==Overview== | ==Overview== | ||
| - | A huge variety of chemically modified oligonucleotide derivatives has been | + | 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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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Declercq, R.]] | [[Category: Declercq, R.]] | ||
| - | [[Category: Meervelt, L | + | [[Category: Meervelt, L Van.]] |
[[Category: dna analogue]] | [[Category: dna analogue]] | ||
[[Category: double helix]] | [[Category: double helix]] | ||
[[Category: hexitol nucleic acid]] | [[Category: hexitol nucleic acid]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 19:12:37 2008'' |
Revision as of 17:12, 21 February 2008
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CRYSTAL STRUCTURE OF A HEXITOL NUCLEIC ACID (HNA) DUPLEX AT 1.6A 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
481D 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
Page seeded by OCA on Thu Feb 21 19:12:37 2008
