Inhibition of eukaryotic translation elongation by cycloheximide and lactimidomycin.
Inhibition of eukaryotic translation elongation by cycloheximide and lactimidomycin.
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DOI：
10.1038/nchembio.304
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发表时间：
2010-03
影响因子：
14.8
通讯作者：
Liu, Jun O.
中科院分区：
文献类型：
--
作者：
Schneider-Poetsch, Tilman;Ju, Jianhua;Eyler, Daniel E.;Dang, Yongjun;Bhat, Shridhar;Merrick, William C.;Green, Rachel;Shen, Ben;Liu, Jun O.
虽然蛋白质合成抑制剂放线菌酮（CHX）已经知道了几十年，其确切的作用机制仍然不完全清楚。CHX的戊二酰亚胺部分见于结构相关的天然产物家族，包括偏头痛抑制素、异米格司他汀和乳酰亚胺霉素（LTM）。发现LTM、异米司他汀和类似物对肿瘤细胞系具有有效的抗增殖作用并选择性抑制蛋白质翻译。对CHX和LTM对蛋白质翻译影响的系统比较研究揭示了两种抑制剂之间的相似性和差异性。发现LTM和CHX都阻断伸长中的易位步骤。足迹实验揭示了在60S核糖体亚基的E位点中的单个胞苷核苷酸（C3993）的保护，从而定义了核糖体中两种抑制剂的共同结合口袋。这些结果为阐明CHX和LTM抑制翻译延伸的分子机制提供了新的线索。
Although the protein synthesis inhibitor cycloheximide (CHX) has been known for decades, its precise mechanism of action remains incompletely understood. The glutarimide portion of CHX is seen in a family of structurally related natural products including migrastatin, isomigrastatin and lactimidomycin (LTM). LTM, isomigrastatin and analogs were found to have a potent antiproliferative effect on tumor cell lines and selectively inhibit protein translation. A systematic comparative study of the effects of CHX and LTM on protein translation revealed both similarities and differences between the two inhibitors. Both LTM and CHX were found to block the translocation step in elongation. Footprinting experiments revealed protection of a single cytidine nucleotide (C3993) in the E-site of the 60S ribosomal subunit, defining a common binding pocket for both inhibitors in the ribosome. These results shed new light on the molecular mechanism of inhibition of translation elongation by both CHX and LTM.
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影响因子：
4.8
作者：
Ledoux, Sarah;Uhlenbeck, Olke C.
通讯作者：
Uhlenbeck, Olke C.
DOI：
10.1073/pnas.0504249102
发表时间：
2005-07-26
影响因子：
11.1
作者：
Bordeleau, ME;Matthews, J;Pelletier, J
通讯作者：
Pelletier, J
影响因子：
64.5
作者：
MOAZED, D;NOLLER, HF
通讯作者：
NOLLER, HF
影响因子：
3.5
作者：
Feng, Zhiyang;Wang, Liyan;Shen, Ben
通讯作者：
Shen, Ben
影响因子：
14.9
作者：
HOLMBERG, L;MELANDER, Y;NYGARD, O
通讯作者：
NYGARD, O