1OKF

NMR structure of an alpha-L-LNA:RNA hybrid

Summary for 1OKF

• Entry DOI: 10.2210/pdb1okf/pdb
• Descriptor: 5'-D(*CP*ATLP*GP*AP*ATLP*AP*ATLP*GP*CP)-3', 5'-R(*GP*CP*AP*UP*AP*UP*CP*AP*GP)-3' (2 entities in total)
• Functional Keywords: dna-rna hybrid, dna/rna hybrid, alpha-l-lna, lna, rna, rnase h, locked nucleic acid
• Total number of polymer chains: 2
• Total formula weight: 5670.61

Authors

Nielsen, J.T.,Stein, P.C.,Petersen, M. (deposition date: 2003-07-23, release date: 2003-10-09, Last modification date: 2024-05-15)

Primary citation

Nielsen, J.T.,Stein, P.C.,Petersen, M.
NMR Structure of an Alpha-L-Lna:RNA Hybrid: Structural Implications for Rnase H Recognition
Nucleic Acids Res., 31:5858-, 2003

PubMed Abstract: Alpha-L-LNA (alpha-L-ribo configured locked nucleic acid) is a nucleotide analogue that raises the thermostability of nucleic acid duplexes by up to approximately 4 degrees C per inclusion. We have determined the NMR structure of a nonamer alpha-L-LNA:RNA hybrid with three alpha-L-LNA modifications. The geometry of this hybrid is intermediate between A- and B-type, all nucleobases partake in Watson-Crick base pairing and base stacking, and the global structure is very similar to that of the corresponding unmodified hybrid. The sugar-phosphate backbone is rearranged in the vicinity of the modified nucleotides. As a consequence, the phosphate groups following the modified nucleotides are rotated into the minor groove. It is interesting that the alpha-L-LNA:RNA hybrid, which has an elevation in melting temperature of 17 degrees C relative to the corresponding DNA:RNA hybrid, retains the global structure of this hybrid. To our knowledge, this is the first example of such a substantial increase in melting temperature of a nucleic acid analogue that does not act as an N-type (RNA) mimic. alpha-L-LNA:RNA hybrids are recognised by RNase H with subsequent cleavage of the RNA strand, albeit with slow rates. We attempt to rationalise this impaired enzyme activity from the rearrangement of the sugar-phosphate backbone of the alpha-L-LNA:RNA hybrid.

PubMed: 14530434
DOI: 10.1093/NAR/GKG800

Experimental method

SOLUTION NMR