Abstract

DNA GYRASE – NEW TARGET FOR ANTITUBERCULAR ACTION.

*Akash Kale, Dr. P. B. Shamkuwar, Akshay Pashte and Aditi Baware

Abstract

Tuberculosis (TB) is one of the deadliest bacterial diseases in the world. New treatment agents must be used as soon as possible to replace existing drugs for which resistance is a severe problem. DNA topoisomerases are well-known targets for chemotherapies that are antibacterial and anticancer. Topoisomerase I in bacteria hasn't yet been exploited as a target for therapeutic antibiotics, despite DNA gyrase being frequently targeted, notably by the very clinically effective fluoroquinolones that have been employed in TB therapy. While treating Mycobacterium tuberculosis (MTB) infection with antibiotics, DNA gyrase is an important nucleoprotein motor found in all bacteria, is a primary target. Gyrase adds negative supercoils to DNA by hydrolyzing ATP utilising a mechanism known as strand passing that has been studied using biophysical and biochemical methods. Bacterial DNA gyrase is one of the key targets of antibacterial drugs like fluoroquinolones. In the majority of bacterial species, fluoroquinolones disrupt DNA gyrase and topoisomerase IV, which causes bacterial cell death. Novobiocin is just one of many other naturally occurring antibacterial compounds that have been shown to be effective against bacteria. The ATP-dependent enzyme DNA gyrase causes an immediate doublestranded DNA break. Being able to catalyse DNA's negative supercoiling, which is required for efficient DNA replication, transcription, and recombination, makes it unique. The DNA gyrase protein is a tetrameric A2B2 protein. The A subunit carries the breakage-reunion active site, whereas the B subunit allows ATP hydrolysis.

Keywords: DNA gyrase, DNA topoisomerase, Fluoroquinolone, negative supercoiling.