1kse
From Proteopedia
(New page: 200px<br /><applet load="1kse" size="450" color="white" frame="true" align="right" spinBox="true" caption="1kse" /> '''Solution Structure of a quinolone-capped DNA...) |
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| - | [[Image:1kse.gif|left|200px]]<br /><applet load="1kse" size=" | + | [[Image:1kse.gif|left|200px]]<br /><applet load="1kse" size="350" color="white" frame="true" align="right" spinBox="true" |
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'''Solution Structure of a quinolone-capped DNA duplex'''<br /> | '''Solution Structure of a quinolone-capped DNA duplex'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Quinolones are gyrase inhibitors that are widely used as antibiotics in | + | Quinolones are gyrase inhibitors that are widely used as antibiotics in the clinic. When covalently attached to oligonucleotides as 5'-acylamido substituents, quinolones were found to stabilize duplexes of oligonucleotides against thermal denaturation. For short duplexes, such as qu-T*GCGCA, where qu is a quinolone residue and T is a 5'-amino-5'-deoxythymidine residue, an increase in the UV melting point of up to 27.8 degrees C was measured. The stabilizing effect was demonstrated for all quinolones tested, namely nalidixic acid, oxolinic acid, pipemidic acid, cinoxacin, norfloxacin, and ofloxacin. The three-dimensional structure of (oa-T*GCGCA)2, where oa is an oxolinic acid residue, was solved by two-dimensional NMR spectroscopy and restrained molecular dynamics. In this complex, the oxolinic acid residues disrupt the terminal T1:A6 base pairs and stack on the G2:C5 base pairs. The displaced adenosine residues bind in the minor groove of the core duplex, while the thymidine residues pack against the oxolinic acid residues. The "molecular cap" thus formed fits tightly on the G:C base pairs, resulting in increased base-pairing fidelity, as demonstrated in UV melting experiments with the sequence oa-T*GGTTGAC and target strands containing a mismatched nucleobase. The structure of the "molecular cap" with its disrupted terminal base pair may also be helpful for modeling how quinolones block re-ligation of DNA strands in the active site of gyrases. |
==About this Structure== | ==About this Structure== | ||
| - | 1KSE is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with OXI as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1KSE is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=OXI:'>OXI</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KSE OCA]. |
==Reference== | ==Reference== | ||
On the effect of covalently appended quinolones on termini of DNA duplexes., Tuma J, Connors WH, Stitelman DH, Richert C, J Am Chem Soc. 2002 Apr 24;124(16):4236-46. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11960452 11960452] | On the effect of covalently appended quinolones on termini of DNA duplexes., Tuma J, Connors WH, Stitelman DH, Richert C, J Am Chem Soc. 2002 Apr 24;124(16):4236-46. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11960452 11960452] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Connors, W | + | [[Category: Connors, W H.]] |
[[Category: Richert, C.]] | [[Category: Richert, C.]] | ||
| - | [[Category: Stitelman, D | + | [[Category: Stitelman, D H.]] |
[[Category: Tuma, J.]] | [[Category: Tuma, J.]] | ||
[[Category: OXI]] | [[Category: OXI]] | ||
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[[Category: synthetic hybrid]] | [[Category: synthetic hybrid]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:37:26 2008'' |
Revision as of 11:37, 21 February 2008
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Solution Structure of a quinolone-capped DNA duplex
Overview
Quinolones are gyrase inhibitors that are widely used as antibiotics in the clinic. When covalently attached to oligonucleotides as 5'-acylamido substituents, quinolones were found to stabilize duplexes of oligonucleotides against thermal denaturation. For short duplexes, such as qu-T*GCGCA, where qu is a quinolone residue and T is a 5'-amino-5'-deoxythymidine residue, an increase in the UV melting point of up to 27.8 degrees C was measured. The stabilizing effect was demonstrated for all quinolones tested, namely nalidixic acid, oxolinic acid, pipemidic acid, cinoxacin, norfloxacin, and ofloxacin. The three-dimensional structure of (oa-T*GCGCA)2, where oa is an oxolinic acid residue, was solved by two-dimensional NMR spectroscopy and restrained molecular dynamics. In this complex, the oxolinic acid residues disrupt the terminal T1:A6 base pairs and stack on the G2:C5 base pairs. The displaced adenosine residues bind in the minor groove of the core duplex, while the thymidine residues pack against the oxolinic acid residues. The "molecular cap" thus formed fits tightly on the G:C base pairs, resulting in increased base-pairing fidelity, as demonstrated in UV melting experiments with the sequence oa-T*GGTTGAC and target strands containing a mismatched nucleobase. The structure of the "molecular cap" with its disrupted terminal base pair may also be helpful for modeling how quinolones block re-ligation of DNA strands in the active site of gyrases.
About this Structure
1KSE is a Protein complex structure of sequences from [1] with as ligand. Full crystallographic information is available from OCA.
Reference
On the effect of covalently appended quinolones on termini of DNA duplexes., Tuma J, Connors WH, Stitelman DH, Richert C, J Am Chem Soc. 2002 Apr 24;124(16):4236-46. PMID:11960452
Page seeded by OCA on Thu Feb 21 13:37:26 2008
