1okf
From Proteopedia
(New page: 200px<br /><applet load="1okf" size="450" color="white" frame="true" align="right" spinBox="true" caption="1okf" /> '''NMR STRUCTURE OF AN ALPHA-L-LNA:RNA HYBRID''...) |
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| - | [[Image:1okf.gif|left|200px]]<br /><applet load="1okf" size=" | + | [[Image:1okf.gif|left|200px]]<br /><applet load="1okf" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1okf" /> | caption="1okf" /> | ||
'''NMR STRUCTURE OF AN ALPHA-L-LNA:RNA HYBRID'''<br /> | '''NMR STRUCTURE OF AN ALPHA-L-LNA:RNA HYBRID'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Alpha-L-LNA (alpha-L-ribo configured locked nucleic acid) is a nucleotide | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1OKF is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http:// | + | 1OKF is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OKF OCA]. |
==Reference== | ==Reference== | ||
NMR structure of an alpha-L-LNA:RNA hybrid: structural implications for RNase H recognition., Nielsen JT, Stein PC, Petersen M, Nucleic Acids Res. 2003 Oct 15;31(20):5858-67. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=14530434 14530434] | NMR structure of an alpha-L-LNA:RNA hybrid: structural implications for RNase H recognition., Nielsen JT, Stein PC, Petersen M, Nucleic Acids Res. 2003 Oct 15;31(20):5858-67. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=14530434 14530434] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Nielsen, J | + | [[Category: Nielsen, J T.]] |
[[Category: Petersen, M.]] | [[Category: Petersen, M.]] | ||
| - | [[Category: Stein, P | + | [[Category: Stein, P C.]] |
[[Category: alpha-l-lna]] | [[Category: alpha-l-lna]] | ||
[[Category: lna]] | [[Category: lna]] | ||
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[[Category: rnase h]] | [[Category: rnase h]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:18:46 2008'' |
Revision as of 12:18, 21 February 2008
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NMR STRUCTURE OF AN ALPHA-L-LNA:RNA HYBRID
Overview
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.
About this Structure
1OKF is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.
Reference
NMR structure of an alpha-L-LNA:RNA hybrid: structural implications for RNase H recognition., Nielsen JT, Stein PC, Petersen M, Nucleic Acids Res. 2003 Oct 15;31(20):5858-67. PMID:14530434
Page seeded by OCA on Thu Feb 21 14:18:46 2008
Categories: Single protein | Nielsen, J T. | Petersen, M. | Stein, P C. | Alpha-l-lna | Lna | Locked nucleic acid | Nmr | Rna | Rnase h
