The tylosin-resistance methyltransferase RlmAII (TlrB) modifies the N-1 position of 23 S rRNA nucleotide G748
The tylosin-resistance methyltransferase RlmAII (TlrB) modifies the N-1 position of 23 S rRNA nucleotide G748
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DOI：
10.1016/j.jmb.2004.02.030
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发表时间：
2004-04-09
影响因子：
5.6
通讯作者：
Poehlsgaard, J
中科院分区：
文献类型：
--
作者：
Douthwaite, S;Crain, PF;Poehlsgaard, J
甲基转移酶RlmA(II)(TlrB)对大环内酯类抗生素泰乐菌素产生抗药性。RlmA(II)对泰乐菌素具有高度特异性，对其他大环内酯类药物或与细菌核糖体上同一区域结合的林可胺和链球菌素B(MLSB)药物不产生耐药性。在本研究中，RlmA(II)的甲基化位点被确定为23个S rRNA核苷酸G748的N-1位。这一位置与泰乐菌素的霉素糖部分接触，这是其他药物所没有的。由m(1)G748赋予的对泰乐菌素的选择性抗药性说明了药物结构的差异如何促进药物在MLSB结合部位的适合性。这一观察结果对于针对MLSB位点的新型抗菌剂的合理设计具有重要意义，特别是如果这些抗菌剂要用于对抗携带m(1)G748的病原体。(C)2004爱思唯尔有限公司。保留所有权利。
The methyltransferase RlmA(II) (TlrB) confers resistance to the macrolide antibiotic tylosin in the drug-producing strain Streptomyces fradiae. The resistance conferred by RlmA(II) is highly specific for tylosin, and no resistance is conferred to other macrolide drugs, or to lincosamide and streptogramin B (MLSB) drugs that bind to the same region on the bacterial ribosome. In this study, the methylation site of RlmA(II) is identified unambiguously by liquid chromatography/electrospray ionization mass spectrometry as the N-1 position of 23 S rRNA nucleotide G748. This position is contacted by the mycinose sugar moiety of tylosin, which is absent from the other drugs. The selective resistance to tylosin conferred by m(1)G748 illustrates how differences in drug structure facilitate the drug fit at the MLSB-binding site. This observation is of relevance for the rational design of novel antimicrobials targeting the MLSB site, especially if the antimicrobials are to be used against pathogens possessing m(1)G748. (C) 2004 Elsevier Ltd. All rights reserved.