THE 24 KDA N-TERMINAL SUBDOMAIN OF THE DNA GYRASE-B PROTEIN BINDS COUMARIN DRUGS
THE 24 KDA N-TERMINAL SUBDOMAIN OF THE DNA GYRASE-B PROTEIN BINDS COUMARIN DRUGS
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DOI：
10.1111/j.1365-2958.1994.tb01026.x
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发表时间：
1994-05-01
影响因子：
3.6
通讯作者：
MAXWELL, A
中科院分区：
文献类型：
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作者：
GILBERT, EJ;MAXWELL, A
许多证据表明，DNA回转酶B蛋白的n端亚结构域包含香豆素抗生素的结合位点。我们已经设计了一个克隆，它编码一个24kDa的蛋白质，代表这个区域。过量产生这种蛋白质的细菌对香豆素的抗性水平升高，表明这种24kda蛋白质在体内与药物结合。在体外，我们发现24kda蛋白不与gyrase A或B蛋白或DNA相互作用，不能水解ATP，也不能与ATP、ADP或ADPNP显著结合。然而，我们发现24kda蛋白与香豆素药物的结合与完整的B蛋白一样紧密。许多实验表明，香豆素与蛋白质的相互作用在本质上主要是疏水的。
A number of lines of evidence suggest that the N-terminal sub-domain of the DNA gyrase B protein contains the binding site for the coumarin antibiotics. We have engineered a clone which encodes a 24kDa protein which represents this domain. Bacteria which overproduce this protein show an elevated level of resistance to coumarins, suggestive of binding of the 24 kDa protein to the drugs in vivo. In vitro we find that the 24 kDa protein does not interact with the gyrase A or B proteins or with DNA, and fails to hydrolyse ATP or show significant binding to ATP, ADP or ADPNP. However, we show that the 24 kDa protein binds coumarin drugs as tightly as the intact B protein. A number of experiments suggest that the interaction of the coumarins with the protein is predominantly hydrophobic in nature.