A steric block in translation caused by the antibiotic spectinomycin

A steric block in translation caused by the antibiotic spectinomycin
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DOI:
10.1021/cb700100n
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发表时间:
2007-08-01
影响因子:
4
通讯作者:
Cate, Jamie H. D.
Cate, Jamie H. D.
中科院分区:
生物学2区
文献类型:
--
作者:
Borovinskaya, Maria A.;Shoji, Shinichiro;Cate, Jamie H. D.

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广泛使用的抗生素大观霉素通过阻断信使RNA的易位和核糖体上的转移RNA来抑制细菌蛋白质的合成。在这里,我们发现在大肠杆菌70S核糖体晶体中,大霉素结合捕获了小核糖体亚基头部结构域的明显旋转状态。大观霉素还能改变体外逆转易位的速率和完整性。这些结构和生化数据表明,在溶液中,大观霉素可以立体阻断小核糖体亚基头部结构域的旋转,从而破坏易位周期。
The widely used antibiotic spectinomycin inhibits bacterial protein synthesis by blocking translocation of messenger RNA and transfer RNAs on the ribosome. Here, we show that in crystals of the Escherichia coli 70S ribosome spectinomycin binding traps a distinct swiveling state of the head domain of the small ribosomal subunit. Spectinomycin also alters the rate and completeness of reverse translocation in vitro. These structural and biochemical data indicate that in solution spectinomycin sterically blocks swiveling of the head domain of the small ribosomal subunit and thereby disrupts the translocation cycle.