481d

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PDB ID 481d

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, resolution 1.60Å
Ligands: , , ,
Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



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

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