Contreras A, Maxwell A
Department of Biochemistry, University of Leicester, UK.
Mol Microbiol. 1992 Jun;6(12):1617-24. doi: 10.1111/j.1365-2958.1992.tb00886.x.
Coumarins are inhibitors of the ATP hydrolysis and DNA supercoiling reactions catalysed by DNA gyrase. Their target is the B subunit of gyrase (GyrB), encoded by the gyrB gene. The exact mode and site of action of the drugs is unknown. We have identified four mutations conferring coumarin resistance to Escherichia coli: Arg-136 to Cys, His or Ser and Gly-164 to Val. In vitro, the ATPase and supercoiling activities of the mutant GyrB proteins are reduced relative to the wild-type enzyme and show resistance to the coumarin antibiotics. Significant differences in the susceptibility of mutant GyrB proteins to inhibition by either chlorobiocin and novobiocin or coumermycin have been found, suggesting wider contacts between coumermycin and GyrB. We discuss the significance of Arg-136 and Gly-164 in relation to the notion that coumarin drugs act as competitive inhibitors of the ATPase reaction.
香豆素是DNA促旋酶催化的ATP水解和DNA超螺旋反应的抑制剂。它们的作用靶点是由gyrB基因编码的促旋酶B亚基（GyrB）。这些药物的确切作用方式和位点尚不清楚。我们已经鉴定出四种赋予大肠杆菌香豆素抗性的突变：Arg-136突变为Cys、His或Ser，以及Gly-164突变为Val。在体外，与野生型酶相比，突变型GyrB蛋白的ATP酶和超螺旋活性降低，并对香豆素类抗生素表现出抗性。已发现突变型GyrB蛋白对氯霉素和新生霉素或香豆霉素抑制作用的敏感性存在显著差异，这表明香豆霉素与GyrB之间存在更广泛的接触。我们讨论了Arg-136和Gly-164与香豆素药物作为ATP酶反应竞争性抑制剂这一概念相关的意义。
