Streptococcus pneumoniae DNA gyrase (DNA gyrase) (DNA gyrase)

Streptococcus pneumoniae DNA gyrase is an essential bacterial enzyme belonging to the type II topoisomerase family, composed of two GyrA and two GyrB subunits (UniProt P0C0V1, P0A4L9). It plays a critical role in maintaining DNA topology by introducing negative supercoils into the bacterial chromosome, which is vital for DNA replication, transcription, and recombination (ASM, 1.2.1). By relieving torsional stress ahead of the replication fork, the enzyme ensures the smooth progression of the replication machinery (NIH, 1.3.1). In the context of disease, Streptococcus pneumoniae is a major human pathogen responsible for pneumonia, meningitis, and sepsis, making its DNA gyrase a primary target for antimicrobial therapy (NIH, 1.4.4). Drugs such as fluoroquinolones bind to the gyrase-DNA complex, trapping it in a covalent intermediate state that leads to lethal double-strand DNA breaks (MDPI, 1.3.4). While fluoroquinolones also target topoisomerase IV in S. pneumoniae, DNA gyrase remains a critical secondary or primary target depending on the specific drug structure (ASM, 1.3.1). However, the clinical utility of these drugs is increasingly challenged by the emergence of resistance mutations within the quinolone resistance-determining regions (QRDRs) of the GyrA and GyrB subunits (NIH, 1.4.3).

Other names

Topoisomerase IIGyrA/GyrB complexDNA topoisomerase (ATP-hydrolyzing)GyrA/GyrB tetramer

Inhibition of DNA gyrase by stabilizing the enzyme-DNA covalent cleavage complex, which prevents DNA re-ligation and results in lethal double-strand DNA breaks.