| Popis: |
Quinolones are a group of low molecular-weight, synthetic and extremely potent antibacterial agents. The functional target of these drugs have been shown to be the bacteria-specific DNA gyrase, a type II DNA topoisomerase. Quinolones may be classified as DNA-targeted drugs in a broader sense, since evidence has been provided that the direct binding target of the drug is the DNA substrate, but not the enzyme. There are two levels of drug binding specificity to pure DNA: (i) at the structure level it binds preferentially to the single-stranded DNA rather than the double-stranded, (ii) at the unpaired nucleotide level the drug binds better to guanine than other bases. At enzyme inhibition level, however, the binding specificity is controlled by the bound enzyme. Although double-stranded relaxed DNA substrate possesses no specific binding site for the drug, the binding of DNA gyrase to the DNA substrate in the presence of ATP has been shown to induce a saturable drug binding site, presumably a partially denatured “bubble” created during the intermediate gate-opening step. These small drug molecules acquire high binding affinity to this specific DNA site through a cooperative binding mechanism that involves self-associations among the drugs as shown by our model. |
