Bacterial DNA gyrase and bacterial topoisomerase IV (Gyrase, Topo IV)

Bacterial DNA gyrase and topoisomerase IV are essential type II topoisomerases in bacteria. DNA gyrase introduces negative supercoils into bacterial DNA and relaxes positive supercoils, an activity essential for DNA replication and transcription. Topoisomerase IV primarily decatenates newly replicated DNA molecules, ensuring proper chromosome segregation during cell division, and also relaxes positive supercoils but does not introduce negative supercoiling[1][3][9]. Both enzymes are heterotetramers made up of A and B type subunits (GyrA/GyrB for gyrase; ParC/ParE or GrlA/GrlB for topo IV, depending on species), and both require ATP hydrolysis for their catalytic cycle[3][5]. They are the primary cellular targets of fluoroquinolone antibiotics, which either stabilize the enzyme-DNA cleavage complex (causing DNA breaks and bacterial cell death) or inhibit ATP binding and enzyme catalytic activity[2][4][6][7]. Resistance emerges primarily through point mutations in the drug-binding sites of their genes. Their centrality to bacterial DNA dynamics and the lack of close eukaryotic homologs make them important and validated targets for antibacterial drug discovery and development[2][4][6][8].

Other names

GyraseType II topoisomerase (bacterial)GyrA/B complexTopo IVParC/ParE (in Gram-negative bacteria)GrlA/GrlB (in Gram-positive bacteria)

Topoisomerase poisons: Drugs (e.g. fluoroquinolones) that stabilize the enzyme-DNA cleavage complex, leading to double-stranded DNA breaks and cell death.\nCatalytic inhibitors: Drugs (e.g. novobiocin) that inhibit ATPase activity required for enzyme function, blocking the supercoiling/decatenation cycle.