DNA gyrase is a type II topoisomerase that can introduce negative supercoils into DNA at the expense of ATP hydrolysis. It is essential in all bacteria but absent from higher eukaryotes, making it an attractive target for antibacterials. The fluoroquinolones are examples of very successful gyrase-targeted drugs, but the rise in bacterial resistance to these agents means that we not only need to seek new compounds, but also new modes of inhibition of this enzyme. We review known gyrase-specific drugs and toxins and assess the prospects for developing new antibacterials targeted to this enzyme.
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http://dx.doi.org/10.1007/s00253-011-3557-z | DOI Listing |
J Biomol Struct Dyn
January 2025
School of Biotechnology, Gautam Buddha University, Greater Noida, Uttar Pradesh, India.
In the realm of hospital-acquired and chronic infections, stands out, demonstrating significant associations with increased morbidity, mortality, and antibiotic resistance. Antibiotic-resistant strains are believed to contribute to thousands of deaths each year. Chronic and latent infections are associated with the bacterial toxin-antitoxin (TA) system, although the mechanisms involved are poorly understood.
View Article and Find Full Text PDFNucleic Acids Res
December 2024
Department of Biology, Massachusetts Institute of Technology, Building 68, 31 Ames St., Cambridge, MA 02139, USA.
The eukaryotic microrchidia (MORC) protein family are DNA gyrase, Hsp90, histidine kinase, MutL (GHKL)-type ATPases involved in gene expression regulation and chromatin compaction. The molecular mechanisms underlying these activities are incompletely understood. Here, we studied the full-length human MORC2 protein biochemically.
View Article and Find Full Text PDFBrief Bioinform
November 2024
Institute of Medical Information, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang District, Beijing 100020, China.
Drug resistance in Mycobacterium tuberculosis (Mtb) is a significant challenge in the control and treatment of tuberculosis, making efforts to combat the spread of this global health burden more difficult. To accelerate anti-tuberculosis drug discovery, repurposing clinically approved or investigational drugs for the treatment of tuberculosis by computational methods has become an attractive strategy. In this study, we developed a virtual screening workflow that combines multiple machine learning and deep learning models, and 11 576 compounds extracted from the DrugBank database were screened against Mtb.
View Article and Find Full Text PDFTrop Med Infect Dis
November 2024
Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea.
Tuberculosis (TB) is a global health challenge associated with considerable levels of illness and mortality worldwide. The development of innovative therapeutic strategies is crucial to combat the rise of drug-resistant TB strains. DNA Gyrase A (GyrA) and serine/threonine protein kinase (PknB) are promising targets for new TB medications.
View Article and Find Full Text PDFEnviron Health (Wash)
December 2024
School of Environmental and Municipal Engineering, Qingdao University of Technology, Qingdao 266520, China.
To clarify the effect of the fluorine atom and piperazine ring on norfloxacin (NOR), NOR degradation products (NOR-DPs, P1-P8) were generated via UV combined with hydrogen peroxide (UV/HO) technology. NOR degradation did not significantly affect cytotoxicity of NOR against BV2, A549, HepG2, and Vero E6 cells. Compared with that of NOR, mutagenicity and median lethal concentration of P1-P8 in fathead minnow were increased, and bioaccumulation factor and oral median lethal dose of P1-P8 in rats were decreased.
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