STUDIES ON THE MODE OF ACTION OF HYGROMYCIN-B, AN INHIBITOR OF TRANSLOCATION IN EUKARYOTES
STUDIES ON THE MODE OF ACTION OF HYGROMYCIN-B, AN INHIBITOR OF TRANSLOCATION IN EUKARYOTES
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DOI：
10.1016/0005-2787(78)90287-3
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发表时间：
1978-01-01
期刊：
影响因子：
--
通讯作者：
SCHINDLER, D
中科院分区：
文献类型：
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作者：
GONZALEZ, A;JIMENEZ, A;SCHINDLER, D
潮霉素B是一种不常见的氨基糖苷类抗生素，对原核细胞和真核细胞均有杀伤作用。潮霉素B浓度为0.38 mM时，可能通过阻止细胞质核糖体合成蛋白质来完全阻止酵母细胞在富含介质中的生长。来自兔网织红细胞、小麦胚芽和酵母的无细胞提取物中的多肽合成被低浓度的潮霉素B强烈阻止。该抗生素通过阻止伸长因子EF-2依赖的易位来抑制酵母多聚体的肽链延长，尽管它不影响EF-2-GTP-核糖体复合体的形成或EF-2和核糖体依赖的GTP水解的发生。潮霉素B对转位的抑制可能是由于结合在核糖体受体部位的多肽-tRNA的稳定，因为在潮霉素B的存在下，[~H]Phe-tRNA-EF-1-聚(U)-核糖体和[~H]Phe-tRNA-聚(U)-核糖体复合体的稳定性增加。网状细胞核糖体对多苯丙氨酸合成的抑制和酵母多聚体对肽-tRNA的酶转位可以通过增加EF-2的浓度而逆转，提示EF-2和潮霉素B在核糖体上的结合部位之间存在关系。在高K浓度下发生的非酶转位和肽键的形成步骤不受潮霉素B的影响。
Hygromycin B is an unusual aminoglycoside antibiotic acitive against prokaryotic and eukaryotic cells. Hygromycin B at 0.38 mM concentration completely halts yeast cell growth in rich media, presumably by preventing protein synthesis by cytoplasmic ribosomes. Polypeptide synthesis in cell-free extracts from rabbit reticulocytes, wheat germ and yeast is strongly blocked by low concentrations of hygromycin B. The antibiotic inhibits peptide chain elongation by yeast polysomes by preventing elongation factor EF-2-dependent translocation, although it does not affect the formation of the EF-2-GTP-ribosome complex or the EF-2- and ribosome-dependent GTP hydrolysis which takes place uncoupled from translocation. The inhibition of translocation by hygromycin B might result from the stabilization of peptidyl-tRNA bound to the ribosomal acceptor site, since the stability of [3H]Phe-tRNA-EF-1-poly(U)-ribosome and [3H]Phe-tRNA-poly(U)-ribosome complexes is increased in the presence of hygromycin B. The inhibition of polyphenylalanine synthesis by reticulocyte ribosomes and enzymic translocation of peptidyl-tRNA by yeast polysomes can be reversed by increasing concentrations of EF-2 suggesting a relationship between the binding sites of EF-2 and hygromycin B on the ribosome. Non-enzymic translocation, that takes place in the presence of high K concentrations and the peptide bond forming step are not affected by hygromycin B.