[Bacterial type II topoisomerases as targets for antibacterial drugs].
Bacterial type II DNA topoisomerases are essential enzymes for correct genome functioning and cell growth. Gyrase is responsible for maintaining negative supercoiling of bacterial chromosome, whereas topoisomerase IV acts in disentangling daughter chromosomes following replication. Type II DNA topoisomerases possess an ATP binding site, which can be treated as a target for antibacterial drugs. Resolving crystal structures of protein fragments consisting of an ATP binding site complexed with ADPNP/antibiotics have proven to be valuable for the understanding of the mode of action of existing antibacterial agents and presented new possibilities for novel drug design. Coumarins, quinolones and cyclothialidines are diverse group of antibiotics that interfere with type II DNA topoisomerases, however their mode of action is different. Recently a new class of antibiotics, simociclinones, was characterized. Their mechanism of action towards gyrase is entirely distinct from already known modes of action, therefore demonstrating the potential for development of novel anti-bacterial agents.
Pietrusiński
Michał
M
Department of Medical Genetics, Medical University of łódź, 1/3 Sterlinga St., 91-425 łódź, Poland.
Staczek
Paweł
P
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000201:enzymology*; D001665:Binding Sites; D004250:DNA Topoisomerases, Type II / Q000187:drug effects* / Q000378:metabolism*; D024881:Drug Resistance, Bacterial; D004791:Enzyme Inhibitors / Q000378:metabolism* / Q000494:pharmacology; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008958:Models, Molecular; D059005:Topoisomerase II Inhibitors
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D059005:Topoisomerase II Inhibitors; D004250:DNA Topoisomerases, Type II