1kse
From Proteopedia
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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 OXI 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
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