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单端孢霉烯族真菌毒素抑制真核生物蛋白质合成的机制

Mechanism of inhibition of eukaryotic protein synthesis by trichothecene fungal toxins.

作者信息

Cundliffe E, Cannon M, Davies J

出版信息

Proc Natl Acad Sci U S A. 1974 Jan;71(1):30-4. doi: 10.1073/pnas.71.1.30.

DOI:10.1073/pnas.71.1.30
PMID:4521056
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC387925/
Abstract

The 12,13-epoxytrichothecenes, a group of sesquiterpenoid fungal antibiotics, inhibit protein synthesis in eukaryotic cells but do not share a common mode of action. Trichodermin stabilizes polyribosomes, prevents their disaggregation by puromycin, and also prevents the release of nascent peptides from ribosomes by puromycin. Nivalenol, T-2 toxin, and verrucarin A cause rapid and almost quantitative breakdown of polyribosomes in H-HeLa cells, a process which is inhibited by anisomycin, cycloheximide, or trichodermin. Similar effects of trichodermin, nivalenol, and verrucarin A are also observed in yeast spheroplasts. We conclude that nivalenol, T-2 toxin, and verrucarin A are potent and highly selective inhibitors of polypeptide chain initiation in eukaryotes, whereas trichodermin inhibits chain elongation and (or) termination. We have compared the structural formulae of various trichothecenes and suggest that the presence of substituents on carbon-15 of the common trichothecene ring may be important in determining the precise modes of action of this group of compounds.

摘要

12,13-环氧单端孢霉烯族毒素是一类倍半萜类真菌抗生素,可抑制真核细胞中的蛋白质合成,但作用方式并不相同。木霉菌素能使多核糖体稳定,阻止其被嘌呤霉素解聚,还能阻止嘌呤霉素从核糖体上释放新生肽。雪腐镰刀菌烯醇、T-2毒素和疣孢菌素A会导致H-HeLa细胞中的多核糖体迅速且几乎完全分解,这一过程会被茴香霉素、环己酰亚胺或木霉菌素抑制。在酵母原生质球中也观察到了木霉菌素、雪腐镰刀菌烯醇和疣孢菌素A的类似作用。我们得出结论,雪腐镰刀菌烯醇、T-2毒素和疣孢菌素A是真核生物中多肽链起始的强效且高度选择性抑制剂,而木霉菌素则抑制链延伸和(或)终止。我们比较了各种单端孢霉烯族毒素的结构式,并表明在常见单端孢霉烯族毒素环的碳-15上存在取代基可能对确定该类化合物的精确作用方式很重要。

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Mechanism of inhibition of eukaryotic protein synthesis by trichothecene fungal toxins.单端孢霉烯族真菌毒素抑制真核生物蛋白质合成的机制
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本文引用的文献

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Inhibition of protein and DNA syntheses in Ehrlich ascites tumour by nivalenol, a toxic principle of Fusarium nivale-growing rice.雪腐镰刀菌烯醇(一种生长在稻谷上的雪腐镰刀菌的毒性成分)对艾氏腹水瘤细胞蛋白质和DNA合成的抑制作用
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Inhibitory effect of nivalenol, a toxic metabolite of Fusarium nivale, on the growth cycle and biopolymer synthesis of HeLa cells.雪腐镰刀菌烯醇(雪腐镰刀菌的一种有毒代谢产物)对HeLa细胞生长周期和生物聚合物合成的抑制作用。
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12,13-Epoxy-delta 9-trichothecenes as the probable mycotoxins responsible for stachybotryotoxicosis.12,13-环氧-δ9-单端孢霉烯族毒素可能是引起葡萄穗霉中毒症的霉菌毒素。
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