1ho6: Difference between revisions

Revision as of 14:03, 21 February 2008

CHIMERIC ARABINONUCLEIC ACID (ANA) HAIRPIN WITH ANA/RNA HYBRID STEM

OverviewOverview

Hybrids of RNA and arabinonucleic acid (ANA) as well as the 2'-fluoro-ANA analog (2'F-ANA) were recently shown to be substrates of the enzyme RNase H. Although RNase H binds to double-stranded RNA, no cleavage occurs with such duplexes. Therefore, knowledge of the structure of ANA/RNA hybrids may prove helpful in the design of future antisense oligonucleotide analogs. In this study, we have determined the NMR solution structures of ANA/RNA and DNA/RNA hairpin duplexes and compared them to the recently published structure of a 2'F-ANA/RNA hairpin duplex. We demonstrate here that the sugars of RNA nucleotides of the ANA/RNA hairpin stem adopt the C3'-endo (north, A-form) conformation, whereas those of the ANA strand adopt a 'rigid' O4'-endo (east) sugar pucker. The DNA strand of the DNA/RNA hairpin stem is flexible, but the average DNA/RNA hairpin structural parameters are close to the ANA/RNA and 2'F-ANA/RNA hairpin parameters. The minor groove width of ANA/RNA, 2'F-ANA/RNA and DNA/RNA helices is 9.0 +/- 0.5 A, a value that is intermediate between that of A- and B-form duplexes. These results rationalize the ability of ANA/RNA and 2'F-ANA/RNA hybrids to elicit RNase H activity.

About this StructureAbout this Structure

1HO6 is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.

ReferenceReference

Solution structure of an arabinonucleic acid (ANA)/RNA duplex in a chimeric hairpin: comparison with 2'-fluoro-ANA/RNA and DNA/RNA hybrids., Denisov AY, Noronha AM, Wilds CJ, Trempe JF, Pon RT, Gehring K, Damha MJ, Nucleic Acids Res. 2001 Nov 1;29(21):4284-93. PMID:11691916

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OCA

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 '''CHIMERIC ARABINONUCLEIC ACID (ANA) HAIRPIN WITH ANA/RNA HYBRID STEM'''<br />
 ==Overview==
-Hybrids of RNA and arabinonucleic acid (ANA) as well as the 2'-fluoro-ANA, analog (2'F-ANA) were recently shown to be substrates of the enzyme RNase, H. Although RNase H binds to double-stranded RNA, no cleavage occurs with, such duplexes. Therefore, knowledge of the structure of ANA/RNA hybrids, may prove helpful in the design of future antisense oligonucleotide, analogs. In this study, we have determined the NMR solution structures of, ANA/RNA and DNA/RNA hairpin duplexes and compared them to the recently, published structure of a 2'F-ANA/RNA hairpin duplex. We demonstrate here, that the sugars of RNA nucleotides of the ANA/RNA hairpin stem adopt the, C3'-endo (north, A-form) conformation, whereas those of the ANA strand, adopt a 'rigid' O4'-endo (east) sugar pucker. The DNA strand of the, DNA/RNA hairpin stem is flexible, but the average DNA/RNA hairpin, structural parameters are close to the ANA/RNA and 2'F-ANA/RNA hairpin, parameters. The minor groove width of ANA/RNA, 2'F-ANA/RNA and DNA/RNA, helices is 9.0 +/- 0.5 A, a value that is intermediate between that of A-, and B-form duplexes. These results rationalize the ability of ANA/RNA and, 2'F-ANA/RNA hybrids to elicit RNase H activity.
+Hybrids of RNA and arabinonucleic acid (ANA) as well as the 2'-fluoro-ANA analog (2'F-ANA) were recently shown to be substrates of the enzyme RNase H. Although RNase H binds to double-stranded RNA, no cleavage occurs with such duplexes. Therefore, knowledge of the structure of ANA/RNA hybrids may prove helpful in the design of future antisense oligonucleotide analogs. In this study, we have determined the NMR solution structures of ANA/RNA and DNA/RNA hairpin duplexes and compared them to the recently published structure of a 2'F-ANA/RNA hairpin duplex. We demonstrate here that the sugars of RNA nucleotides of the ANA/RNA hairpin stem adopt the C3'-endo (north, A-form) conformation, whereas those of the ANA strand adopt a 'rigid' O4'-endo (east) sugar pucker. The DNA strand of the DNA/RNA hairpin stem is flexible, but the average DNA/RNA hairpin structural parameters are close to the ANA/RNA and 2'F-ANA/RNA hairpin parameters. The minor groove width of ANA/RNA, 2'F-ANA/RNA and DNA/RNA helices is 9.0 +/- 0.5 A, a value that is intermediate between that of A- and B-form duplexes. These results rationalize the ability of ANA/RNA and 2'F-ANA/RNA hybrids to elicit RNase H activity.
 ==About this Structure==
-HO6 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=1HO6 OCA].
+HO6 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=1HO6 OCA].
 ==Reference==
 Solution structure of an arabinonucleic acid (ANA)/RNA duplex in a chimeric hairpin: comparison with 2'-fluoro-ANA/RNA and DNA/RNA hybrids., Denisov AY, Noronha AM, Wilds CJ, Trempe JF, Pon RT, Gehring K, Damha MJ, Nucleic Acids Res. 2001 Nov 1;29(21):4284-93. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11691916 11691916]
 [[Category: Protein complex]]
-[[Category: Denisov, A.Y.]]
+[[Category: Denisov, A Y.]]
 [[Category: Gehring, K.]]
 [[Category: arabinonucleic acid]]
@@ Line 18: / Line 18: @@
 [[Category: rna]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sun Nov 25 02:50:02 2007''
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