The interaction between coumarin drugs and DNA gyrase.
The coumarin group of antibiotics have as their target the bacterial enzyme DNA gyrase. The drugs bind to the B subunit of gyrase and inhibit DNA supercoiling by blocking the ATPase activity. Recent data show that the binding site for the drugs lies within the N-terminal part of the B protein, and individual amino acids involved in coumarin interaction are being identified. The mode of inhibition of the gyrase ATPase reaction by coumarins is unlikely to be simple competitive inhibition, and the drugs may act by stabilizing a conformation of the enzyme with low affinity for ATP.
Maxwell
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Department of Biochemistry, University of Leicester, UK.
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D049933:Aminocoumarins; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D003374:Coumarins / Q000378:metabolism / Q000494:pharmacology; D004250:DNA Topoisomerases, Type II / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004269:DNA, Bacterial / Q000378:metabolism; D004278:DNA, Superhelical / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D008958:Models, Molecular; D009675:Novobiocin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors
D049933:Aminocoumarins; D001426:Bacterial Proteins; D003374:Coumarins; D004269:DNA, Bacterial; D004278:DNA, Superhelical; D059005:Topoisomerase II Inhibitors; D009675:Novobiocin; C006260:clorobiocin; D000251:Adenosine Triphosphatases; D004250:DNA Topoisomerases, Type II; C004628:coumermycin