Question

Explain why compounds that inhibit the activity of bacterial topoisomerase are used as antibiotics.

Answer 1

DNA topoisomerases are enzymes that regulate DNA topology and are essential for the integrity of the genetic material during transcription,replication and recombination processes.Topoisomerase I cuts a single strand of the DNA double helix while topoisomerase II cuts both strands of DNA,using ATP for fuel.The uncoiling process involves the relaxation of the coil of both DNA strands.After the cuts are made and replication or repair is complete,the strands are paired back together and the coil reforms.The topoisomerase enzymes are considered targets for the generation of new cancer treatments because when they are inhibited in a cell,the cell dies.Inhibitors of the topoisomerase enzymes have the ability to kill cells undergoing DNA replication,stop reading of the DNA for protein production, and stop repair of DNA damage.Since cancer cells divide much more rapidly than normal cells,the cancer cells will be killed disproportionately by the topoisomerase inhibitors,though some normal cells with topoisomerase activity will also be killed.Topoisomerase II inhibitors are considered as poisons which target the topoisomerase-DNA complexand topoisomerase inhibitors,which disrupt catalytic turnover.Topoisomerase I and II inhibitors work by binding to the topoisomerase enzyme molecule.This blocks the ability of the topoisomerase to bind the DNA back together after it has been cut,thereby making the enzyme nonfunctional.