Amicoumacin a inhibits translation by stabilizing mRNA interaction with the ribosome.
Amicoumacin a inhibits translation by stabilizing mRNA interaction with the ribosome.
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DOI：
10.1016/j.molcel.2014.09.020
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发表时间：
2014-11-20
期刊：
影响因子：
16
通讯作者：
Sergiev PV
中科院分区：
文献类型：
--
作者：
Polikanov YS;Osterman IA;Szal T;Tashlitsky VN;Serebryakova MV;Kusochek P;Bulkley D;Malanicheva IA;Efimenko TA;Efremenkova OV;Konevega AL;Shaw KJ;Bogdanov AA;Rodnina MV;Dontsova OA;Mankin AS;Steitz TA;Sergiev PV
我们证明，细胞靶标未知的抗生素阿米古星 A (AMI) 是一种有效的蛋白质合成抑制剂。 16S rRNA 螺旋 24 中的抗性突变将 AMI 结合位点映射到小核糖体亚基。以 2.4 Å 分辨率解析的细菌核糖体与 AMI 复合物的晶体结构表明，抗生素与 16S rRNA 的 E 位点和 mRNA 主链中普遍保守的核苷酸接触。 AMI 与 16S rRNA 和 mRNA 的同时相互作用以及体内实验证据表明，它可能抑制核糖体沿着 mRNA 的进展。与该提议一致，AMI 的结合干扰体外易位。 AMI 的抑制作用可以通过翻译延伸因子 G 的突变得到部分补偿。
We demonstrate that the antibiotic amicoumacin A (AMI) whose cellular target was unknown, is a potent inhibitor of protein synthesis. Resistance mutations in helix 24 of the 16S rRNA mapped the AMI binding site to the small ribosomal subunit. The crystal structure of bacterial ribosome in complex with AMI solved at 2.4 Å resolution revealed that the antibiotic makes contacts with universally conserved nucleotides of 16S rRNA in the E site and the mRNA backbone. Simultaneous interactions of AMI with 16S rRNA and mRNA and the in vivo experimental evidence suggest that it may inhibit the progression of the ribosome along mRNA. Consistent with this proposal, binding of AMI interferes with translocation in vitro. The inhibitory action of AMI can be partly compensated by mutations in the translation elongation factor G.