The ATP-binding site of type II topoisomerases as a target for antibacterial drugs.
DNA topoisomerases are essential enzymes in all cell types and have been found to be valuable drug targets both for antibacterial and anti-cancer chemotherapy. Type II topoisomerases possess a binding site for ATP, which can be exploited as a target for chemo-therapeutic agents. High-resolution structures of protein fragments containing this site complexed with antibiotics or an ATP analogue have provided vital information for the understanding of the action of existing drugs and for the potential development of novel anti-bacterial agents. In this article we have reviewed the structure and function of the ATPase domain of DNA gyrase (bacterial topoisomerase II), particularly highlighting novel information that has been revealed by structural studies. We discuss the efficacy and mode of action of existing drugs and consider the prospects for the development of novel agents.
Maxwell
Anthony
A
Department of Biological Chemistry, John Innes Centre, Norwich Research Park, Colney, UK. tony.maxwell@bbsrc.ac.uk
Lawson
David M
DM
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000890:Anti-Infective Agents / Q000378:metabolism* / Q000494:pharmacology; D001665:Binding Sites; D004250:DNA Topoisomerases, Type II / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism* / Q000494:pharmacology; D006868:Hydrolysis; D008958:Models, Molecular
D000890:Anti-Infective Agents; D004791:Enzyme Inhibitors; D000255:Adenosine Triphosphate; D004250:DNA Topoisomerases, Type II