149d
From Proteopedia
(New page: 200px<br /><applet load="149d" size="450" color="white" frame="true" align="right" spinBox="true" caption="149d" /> '''SOLUTION STRUCTURE OF A PYRIMIDINE(DOT)PURIN...) |
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caption="149d" /> | caption="149d" /> | ||
'''SOLUTION STRUCTURE OF A PYRIMIDINE(DOT)PURINE(DOT) PYRIMIDINE DNA TRIPLEX CONTAINING T(DOT)AT, C+(DOT)GC AND G(DOT)TA TRIPLES'''<br /> | '''SOLUTION STRUCTURE OF A PYRIMIDINE(DOT)PURINE(DOT) PYRIMIDINE DNA TRIPLEX CONTAINING T(DOT)AT, C+(DOT)GC AND G(DOT)TA TRIPLES'''<br /> | ||
==Overview== | ==Overview== | ||
| - | BACKGROUND: Under certain conditions, homopyrimidine oligonucleotides can | + | BACKGROUND: Under certain conditions, homopyrimidine oligonucleotides can bind to complementary homopurine sequences in homopurine-homopyrimidine segments of duplex DNA to form triple helical structures. Besides having biological implications in vivo, this property has been exploited in molecular biology applications. This approach is limited by a lack of knowledge about the recognition by the third strand of pyrimidine residues in Watson-Crick base pairs. RESULTS: We have therefore determined the solution structure of a pyrimidine.purine.pyrimidine (Y.RY) DNA triple helix containing a guanine residue in the third strand which was postulated to specifically recognize a thymine residue in a Watson-Crick TA base pair. The structure was solved by combining NMR-derived restraints with molecular dynamics simulations conducted in the presence of explicit solvent and counter ions. The guanine of the G-TA triple is tilted out of the plane of its target TA base pair towards the 3'-direction, to avoid a steric clash with the thymine methyl group. This allows the guanine amino protons to participate in hydrogen bonds with separate carbonyls, forming one strong bond within the G-TA triple and a weak bond to an adjacent T.AT triple. Dramatic variations in helical twist around the guanine residue lead to a novel stacking interaction. At the global level, the Y.RY DNA triplex shares several structural features with the recently solved solution structure of the R.RY DNA triplex. CONCLUSIONS: The formation of a G.TA triple within an otherwise pyrimidine.purine.pyrimidine DNA triplex causes conformational realignments in and around the G.TA triple. These highlight new aspects of molecular recognition that could be useful in triplex-based approaches to inhibition of gene expression and site-specific cleavage of genomic DNA. |
==About this Structure== | ==About this Structure== | ||
| - | 149D 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:// | + | 149D 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=149D OCA]. |
==Reference== | ==Reference== | ||
Solution structure of a pyrimidine.purine.pyrimidine DNA triplex containing T.AT, C+.GC and G.TA triples., Radhakrishnan I, Patel DJ, Structure. 1994 Jan 15;2(1):17-32. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=8075980 8075980] | Solution structure of a pyrimidine.purine.pyrimidine DNA triplex containing T.AT, C+.GC and G.TA triples., Radhakrishnan I, Patel DJ, Structure. 1994 Jan 15;2(1):17-32. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=8075980 8075980] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Patel, D | + | [[Category: Patel, D J.]] |
[[Category: Radhakrishnan, I.]] | [[Category: Radhakrishnan, I.]] | ||
[[Category: dna]] | [[Category: dna]] | ||
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[[Category: triplex]] | [[Category: triplex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:38:19 2008'' |
Revision as of 09:38, 21 February 2008
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SOLUTION STRUCTURE OF A PYRIMIDINE(DOT)PURINE(DOT) PYRIMIDINE DNA TRIPLEX CONTAINING T(DOT)AT, C+(DOT)GC AND G(DOT)TA TRIPLES
Overview
BACKGROUND: Under certain conditions, homopyrimidine oligonucleotides can bind to complementary homopurine sequences in homopurine-homopyrimidine segments of duplex DNA to form triple helical structures. Besides having biological implications in vivo, this property has been exploited in molecular biology applications. This approach is limited by a lack of knowledge about the recognition by the third strand of pyrimidine residues in Watson-Crick base pairs. RESULTS: We have therefore determined the solution structure of a pyrimidine.purine.pyrimidine (Y.RY) DNA triple helix containing a guanine residue in the third strand which was postulated to specifically recognize a thymine residue in a Watson-Crick TA base pair. The structure was solved by combining NMR-derived restraints with molecular dynamics simulations conducted in the presence of explicit solvent and counter ions. The guanine of the G-TA triple is tilted out of the plane of its target TA base pair towards the 3'-direction, to avoid a steric clash with the thymine methyl group. This allows the guanine amino protons to participate in hydrogen bonds with separate carbonyls, forming one strong bond within the G-TA triple and a weak bond to an adjacent T.AT triple. Dramatic variations in helical twist around the guanine residue lead to a novel stacking interaction. At the global level, the Y.RY DNA triplex shares several structural features with the recently solved solution structure of the R.RY DNA triplex. CONCLUSIONS: The formation of a G.TA triple within an otherwise pyrimidine.purine.pyrimidine DNA triplex causes conformational realignments in and around the G.TA triple. These highlight new aspects of molecular recognition that could be useful in triplex-based approaches to inhibition of gene expression and site-specific cleavage of genomic DNA.
About this Structure
149D is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.
Reference
Solution structure of a pyrimidine.purine.pyrimidine DNA triplex containing T.AT, C+.GC and G.TA triples., Radhakrishnan I, Patel DJ, Structure. 1994 Jan 15;2(1):17-32. PMID:8075980
Page seeded by OCA on Thu Feb 21 11:38:19 2008
Categories: Protein complex | Patel, D J. | Radhakrishnan, I. | Dna | Nmr | Triplex
