1x26: Difference between revisions

From Proteopedia
Jump to navigationJump to search
OCA (talk | contribs)
New page: left|200px<br /><applet load="1x26" size="450" color="white" frame="true" align="right" spinBox="true" caption="1x26" /> '''Solution structure of the AA-mismatch DNA co...
 
OCA (talk | contribs)
No edit summary
Line 1: Line 1:
[[Image:1x26.gif|left|200px]]<br /><applet load="1x26" size="450" color="white" frame="true" align="right" spinBox="true"  
[[Image:1x26.gif|left|200px]]<br /><applet load="1x26" size="350" color="white" frame="true" align="right" spinBox="true"  
caption="1x26" />
caption="1x26" />
'''Solution structure of the AA-mismatch DNA complexed with naphthyridine-azaquinolone'''<br />
'''Solution structure of the AA-mismatch DNA complexed with naphthyridine-azaquinolone'''<br />


==Overview==
==Overview==
DNA trinucleotide repeats, particularly CXG, are common within the human, genome. However, expansion of trinucleotide repeats is associated with a, number of disorders, including Huntington disease, spinobulbar muscular, atrophy and spinocerebellar ataxia. In these cases, the repeat length is, known to correlate with decreased age of onset and disease severity., Repeat expansion of (CAG)n, (CTG)n and (CGG)n trinucleotides may be, related to the increased stability of alternative DNA hairpin structures, consisting of CXG-CXG triads with X-X mismatches. Small-molecule ligands, that selectively bound to CAG repeats could provide an important probe for, determining repeat length and an important tool for investigating the in, vivo repeat extension mechanism. Here we report that, napthyridine-azaquinolone (NA, 1) is a ligand for CAG repeats and can be, used as a diagnostic tool for determining repeat length. We show by NMR, spectroscopy that binding of NA to CAG repeats induces the extrusion of a, cytidine nucleotide from the DNA helix.
DNA trinucleotide repeats, particularly CXG, are common within the human genome. However, expansion of trinucleotide repeats is associated with a number of disorders, including Huntington disease, spinobulbar muscular atrophy and spinocerebellar ataxia. In these cases, the repeat length is known to correlate with decreased age of onset and disease severity. Repeat expansion of (CAG)n, (CTG)n and (CGG)n trinucleotides may be related to the increased stability of alternative DNA hairpin structures consisting of CXG-CXG triads with X-X mismatches. Small-molecule ligands that selectively bound to CAG repeats could provide an important probe for determining repeat length and an important tool for investigating the in vivo repeat extension mechanism. Here we report that napthyridine-azaquinolone (NA, 1) is a ligand for CAG repeats and can be used as a diagnostic tool for determining repeat length. We show by NMR spectroscopy that binding of NA to CAG repeats induces the extrusion of a cytidine nucleotide from the DNA helix.


==About this Structure==
==About this Structure==
1X26 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with NAZ as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1X26 OCA].  
1X26 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=NAZ:'>NAZ</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1X26 OCA].  


==Reference==
==Reference==
Line 27: Line 27:
[[Category: drug]]
[[Category: drug]]


''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sun Nov 25 01:18:30 2007''
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:50:18 2008''