ERYTHROMYCIN, CARBOMYCIN, AND SPIRAMYCIN INHIBIT PROTEIN-SYNTHESIS BY STIMULATING THE DISSOCIATION OF PEPTIDYL-TRANSFER RNA FROM RIBOSOMES
ERYTHROMYCIN, CARBOMYCIN, AND SPIRAMYCIN INHIBIT PROTEIN-SYNTHESIS BY STIMULATING THE DISSOCIATION OF PEPTIDYL-TRANSFER RNA FROM RIBOSOMES
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DOI：
10.1128/aac.21.5.811
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发表时间：
1982-01-01
影响因子：
4.9
通讯作者：
OTTO, DP
中科院分区：
文献类型：
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作者：
MENNINGER, JR;OTTO, DP
在带有温度敏感型多肽-tRNA水解酶(氨基酰基-tRNA水解酶；EC 3.1.1.29)的突变大肠杆菌中，多肽-tRNA在不允许的温度(40℃)下积累。C)细胞死亡。如果首先用红霉素、卡莫霉素或螺旋霉素处理细胞，剂量足以抑制野生型细胞的蛋白质合成，但不足以在允许的温度(30度)下杀死突变或野生型细胞，则高温的这些后果会加剧。c)。由于突变细胞中的肽基-tRNA水解酶在40℃时迅速失活且不可逆。在抗生素的刺激下，核糖体中肽-tRNA的解离增强，从而促进了肽-tRNA的积累和杀伤。讨论了这些发现对于抑制细胞生长和蛋白质合成的意义。某些备选解释被证明与相关数据不一致。以前关于大环内酯类抗生素效果的相互矛盾的观察结果是根据这些观察结果进行解释的。显然，红霉素、卡莫霉素和螺旋霉素(可能还有所有大环内酯类化合物)的主要作用机制是刺激肽-tRNA从核糖体中解离，可能是在转位过程中。
In mutant Escherichia coli with temperature-sensitive peptidyl-tRNA hydrolase (aminoacyl-tRNA hydrolase; EC 3.1.1.29), peptidyl-tRNA accumulates at the nonpermissive temperature (40.degree. C) and the cells die. These consequences of high temperature were enhanced if the cells were first treated with erythromycin, carbomycin or spiramycin at doses sufficient to inhibit protein synthesis in wild-type cells but not sufficient to kill mutant or wild-type cells at the permissive temperature (30.degree. C). Since peptidyl-tRNA hydrolase in the mutant cells is inactivated rapidly and irreversibly at 40.degree. C, the enhanced accumulation of peptidyl-tRNA and killing were the result of enhanced dissociation, stimulated by the antibiotics, of peptidyl-tRNA from ribosomes. The implications of these findings for inhibition of cell growth and protein synthesis are discussed. Certain alternative interpretations are shown to be inconsistent with the relevant data. Previous conflicting observations on the effects of macrolide antibiotics are explained in terms of these observations. Evidently, erythromycin, carbomycin and spiramycin (and probably all macrolides) have as a primary mechanism of action the stimulation of dissociation of peptidyl-tRNA from ribosomes, probably during translocation.