NEW ANTIBIOTIC THAT ACTS SPECIFICALLY ON THE GTP-BOUND FORM OF ELONGATION FACTOR-TU
NEW ANTIBIOTIC THAT ACTS SPECIFICALLY ON THE GTP-BOUND FORM OF ELONGATION FACTOR-TU
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DOI：
10.1002/j.1460-2075.1991.tb08009.x
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发表时间：
1991-04-01
期刊：
影响因子：
11.4
通讯作者：
PARMEGGIANI, A
中科院分区：
文献类型：
--
作者：
ANBORGH, PH;PARMEGGIANI, A
新的噻唑基肽抗生素GE 2270 A，从玫瑰花平双孢菌菌株ATCC 53773中分离，显示通过特异性影响GTP结合形式的延伸因子Tu（EF-Tu）来抑制细菌蛋白质的体外生物合成。 EF-Tu.GTP的“关闭”速率减慢400倍，将GTP锁定在EF-Tu上，而EF-Tu.GDP不受影响。 因此，在EF-Tu.鸟嘌呤核苷酸相互作用上，GE 2270 A模拟aa-tRNA的作用。 与此一致，抗生素阻碍了aa-tRNA与EF-Tu.GTP的结合，如不存在稳定的三元复合物和抑制aa-tRNA与核糖体的酶结合所示。 这会阻断伸长周期。GE 2270 A基本上不改变EF-Tu的内在GT3活性，但削弱了该反应的核糖体刺激。 GE 2270 A对EF-Tu.GTP与aa-tRNA相互作用的负效应与结构无关的普沃霉素相似，而比较这两种抗生素对EF-Tu. GDP的作用则有显著差异。 这项工作强调了各种过渡构象的调整EF-Tu与GTP和GDP的相互作用。
The new thiazolyl peptide antibiotic GE2270 A, isolated from Planobispora rosea strain ATCC 53773, is shown to inhibit bacterial protein biosynthesis in vitro by affecting specifically the GTP-bound form of elongation factor Tu (EF-Tu). The 'off' rate of EF-Tu.GTP is slowed down 400-fold, locking GTP on EF-Tu, whereas EF-Tu.GDP is unaffected. Therefore, on the EF-Tu.guanine nucleotide interaction, GE2270 A mimics the effect of aa-tRNA. In line with this, the binding of aa-tRNA to EF-Tu.GTP is hindered by the antibiotic, as shown by the absence of a stable ternary complex and the inhibition of the enzymatic binding of aa-tRNA to the ribosome. This blocks the elongation cycle. GE2270 A does not essentially modify the intrinsic GTPase activity of EF-Tu, but impairs the stimulation by ribosomes of this reaction. The negative effect of GE2270 A on the EF-Tu.GTP interaction with aa-tRNA bears similarities with that of the structurally unrelated pulvomycin, whereas marked differences were found by comparing the effects of these two antibiotics on EF-Tu.GDP. This work emphasizes the varieties of the transitional conformations which tune the EF-Tu interaction with GTP and GDP.