THE F-PLASMID CCDB PROTEIN INDUCES EFFICIENT ATP-DEPENDENT DNA CLEAVAGE BY GYRASE
THE F-PLASMID CCDB PROTEIN INDUCES EFFICIENT ATP-DEPENDENT DNA CLEAVAGE BY GYRASE
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DOI：
10.1006/jmbi.1993.1609
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发表时间：
1993-12-05
影响因子：
5.6
通讯作者：
COUTURIER, M
中科院分区：
文献类型：
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作者：
BERNARD, P;KEZDY, KE;COUTURIER, M
DNA拓扑异构酶在DNA复制、基因转录和染色体分离中起重要作用。最近，我们发现了一种新的拓扑异构酶Ⅱ毒素：质粒F的CCdB蛋白。当它的作用不被CcdA蛋白阻止时，CcdB蛋白是一种有效的将促旋酶捕获在可切割复合物中的蛋白。CcdA蛋白不仅是CcdB蛋白，还有效地将促旋酶捕获在可清除的复合物中。CcdA蛋白不仅阻止CcdB的促旋酶中毒活性，而且逆转其对促旋酶的作用。CcdB蛋白诱导DNA链断裂的机制与喹诺酮类抗生素的作用密切相关。然而，CcdB裂解过程的ATP依赖性将CcdB机制与喹诺酮依赖性反应区分开来，因为喹诺酮类抗生素刺激有效的DNA断裂，无论ATP是否存在。我们以前的研究表明，对喹诺酮类抗生素耐药的细菌对CcdB敏感，反之亦然。阐明CcdB蛋白的作用机制可能有助于设计针对促旋酶的药物，以利用这种新的中毒机制。
DNA topoisomerases perform essential roles in DNA replication, gene transcription, and chromosome segregation. Recently, we identified a new type of topoisomerase II poison: the CCdB protein of plasmid F. When its action is not prevented by CcdA protein, the CcdB protein is a potent efficiently traps gyrase in a cleavable complex. The CcdA protein not only that CcdB protein efficiently traps gyrase in a clearable complex. The CcdA protein not only prevents the gyrase poisoning activity of CcdB but also reverses its effect on gyrase. The mechanism by which the CcdB protein induces DNA strand breakage is closely related to the action of quinolone antibiotics. However, the ATP dependence of the CcdB cleavage process differentiates the CcdB mechanism from quinolone-dependent reactions because the quinolone antibiotics stimulate efficient DNA breakage, whether or not ATP is present. We previously showed that bacteria resistant to quinolone antibiotics are sensitive to CcdB andvice versa. Elucidation of the mechanism of action of CcdB protein may permit the design of drugs targeting gyrase so as to take advantage of this new poisoning mechanism.