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病原体衍生的氨基糖苷类耐药16S rRNA甲基转移酶NpmA具有双重m1A1408/m1G1408特异性。

The Pathogen-Derived Aminoglycoside Resistance 16S rRNA Methyltransferase NpmA Possesses Dual m1A1408/m1G1408 Specificity.

作者信息

Zelinskaya Natalia, Witek Marta A, Conn Graeme L

机构信息

Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, USA.

Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, USA

出版信息

Antimicrob Agents Chemother. 2015 Dec;59(12):7862-5. doi: 10.1128/AAC.01872-15. Epub 2015 Sep 28.

DOI:10.1128/AAC.01872-15
PMID:26416864
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4649141/
Abstract

Chemical modification of 16S rRNA can confer exceptionally high-level resistance to a diverse set of aminoglycoside antibiotics. Here, we show that the pathogen-derived enzyme NpmA possesses dual m(1)A1408/m(1)G1408 activity, an unexpected property apparently unique among the known aminoglycoside resistance 16S rRNA (m(1)A1408) methyltransferases. Although the biological significance of this activity remains to be determined, such mechanistic variation in enzymes acquired by pathogens has significant implications for development of inhibitors of these emerging resistance determinants.

摘要

16S rRNA的化学修饰可赋予对多种氨基糖苷类抗生素极高水平的抗性。在此,我们表明病原体来源的酶NpmA具有双重m(1)A1408/m(1)G1408活性,这一意外特性在已知的氨基糖苷类抗性16S rRNA(m(1)A1408)甲基转移酶中显然是独特的。尽管这种活性的生物学意义仍有待确定,但病原体获得的酶的这种机制变异对这些新出现的抗性决定因素的抑制剂开发具有重要意义。

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本文引用的文献

1
30S Subunit-dependent activation of the Sorangium cellulosum So ce56 aminoglycoside resistance-conferring 16S rRNA methyltransferase Kmr.嗜热栖热放线菌So ce56赋予氨基糖苷抗性的16S rRNA甲基转移酶Kmr依赖30S亚基的激活
Antimicrob Agents Chemother. 2015 May;59(5):2807-16. doi: 10.1128/AAC.00056-15. Epub 2015 Mar 2.
2
Expansion of the aminoglycoside-resistance 16S rRNA (m(1)A1408) methyltransferase family: expression and functional characterization of four hypothetical enzymes of diverse bacterial origin.氨基糖苷抗性16S rRNA(m(1)A1408)甲基转移酶家族的扩展:来自不同细菌来源的四种假定酶的表达及功能表征
Biochim Biophys Acta. 2014 Sep;1844(9):1648-55. doi: 10.1016/j.bbapap.2014.06.012. Epub 2014 Jun 22.
3
Molecular recognition and modification of the 30S ribosome by the aminoglycoside-resistance methyltransferase NpmA.氨基糖苷类耐药甲基转移酶 NpmA 对 30S 核糖体的分子识别与修饰。
Proc Natl Acad Sci U S A. 2014 Apr 29;111(17):6275-80. doi: 10.1073/pnas.1402789111. Epub 2014 Apr 9.
4
Exogenously acquired 16S rRNA methyltransferases found in aminoglycoside-resistant pathogenic Gram-negative bacteria: an update.氨基糖苷类耐药的致病性革兰氏阴性菌中发现的外源性获得的 16S rRNA 甲基转移酶:最新进展。
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5
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Determination of the target nucleosides for members of two families of 16S rRNA methyltransferases that confer resistance to partially overlapping groups of aminoglycoside antibiotics.确定两类16S rRNA甲基转移酶成员的靶标核苷,这两类酶赋予对部分重叠的氨基糖苷类抗生素组的抗性。
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