DNA gyrase subunit A and topoisomerase IV subunit A (GyrA and ParC)

DNA gyrase subunit A (GyrA) and topoisomerase IV subunit A (ParC) are the DNA-binding and catalytically active protein subunits of two essential type II topoisomerases found in bacteria. DNA gyrase is unique in its ability to introduce negative supercoils into bacterial DNA, an activity critical for managing DNA topology and facilitating replication and transcription[7]. Topoisomerase IV, in contrast, primarily decatenates intertwined daughter chromosomes following DNA replication, enabling chromosome segregation prior to cell division[2][1][5][6]. Both enzymes are heterotetrameric complexes: gyrase is composed of two GyrA and two GyrB subunits; topoisomerase IV comprises two ParC and two ParE subunits[2][5][7][8]. These enzymes are vital for bacterial viability and are well-established targets for major antibacterial drugs, especially fluoroquinolones, which exert their effects by stabilizing double-stranded DNA breaks within the enzyme-DNA complex, ultimately leading to cell death[6][8]. Mutations in gyrA or parC result in bacterial resistance to these drugs, posing a significant challenge in clinical settings[6][8].Both subunits play distinct but complementary roles: - **GyrA**: catalyzes negative supercoil introduction, essential for DNA compaction and topology[7]. - **ParC**: catalyzes DNA decatenation after replication, essential for proper chromosome segregation[1][2][5][6].Their critical functions in DNA metabolism and their established druggability make them key molecular targets in antibacterial therapy.

Other names

GyrADNA topoisomerase II subunit AParCGrlADNA topoisomerase IV subunit A

Inhibition of DNA breakage and religation during topological change, often by stabilizing DNA-enzyme cleavage complexes (fluoroquinolones); ATP-binding inhibition (aminocoumarins)