文章基本信息

标题：Structural basis of a histidine-DNA nicking/joining mechanism for gene transfer and promiscuous spread of antibiotic resistance
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作者：Radoslaw Pluta ; D. Roeland Boer ; Fabián Lorenzo-Díaz 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2017
卷号：114
期号：32
页码：E6526-E6535
DOI：10.1073/pnas.1702971114
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Relaxases are metal-dependent nucleases that break and join DNA for the initiation and completion of conjugative bacterial gene transfer. Conjugation is the main process through which antibiotic resistance spreads among bacteria, with multidrug-resistant staphylococci and streptococci infections posing major threats to human health. The MOB_V family of relaxases accounts for approximately 85% of all relaxases found in Staphylococcus aureus isolates. Here, we present six structures of the MOB_V relaxase MobM from the promiscuous plasmid pMV158 in complex with several origin of transfer DNA fragments. A combined structural, biochemical, and computational approach reveals that MobM follows a previously uncharacterized histidine/metal-dependent DNA processing mechanism, which involves the formation of a covalent phosphoramidate histidine-DNA adduct for cell-to-cell transfer. We discuss how the chemical features of the high-energy phosphorus-nitrogen bond shape the dominant position of MOB_V histidine relaxases among small promiscuous plasmids and their preference toward Gram-positive bacteria.
关键词：histidine relaxase ; antibiotic resistance ; horizontal gene transfer ; X-ray structure ; Staphylococcus aureus