文章基本信息

标题：Structure of Pseudomonas aeruginosa ribosomes from an aminoglycoside-resistant clinical isolate
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作者：Yehuda Halfon ; Alicia Jimenez-Fernandez ; Ruggero La Rosa 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：2019
卷号：116
期号：44
页码：22275-22281
DOI：10.1073/pnas.1909831116
出版社：The National Academy of Sciences of the United States of America
摘要：Resistance to antibiotics has become a major threat to modern medicine. The ribosome plays a fundamental role in cell vitality by the translation of the genetic code into proteins; hence, it is a major target for clinically useful antibiotics. We report here the cryo-electron microscopy structures of the ribosome of a pathogenic aminoglycoside (AG)-resistant Pseudomonas aeruginosa strain, as well as of a nonresistance strain isolated from a cystic fibrosis patient. The structural studies disclosed defective ribosome complex formation due to a conformational change of rRNA helix H69, an essential intersubunit bridge, and a secondary binding site of the AGs. In addition, a stable conformation of nucleotides A1486 and A1487, pointing into helix h44, is created compared to a non-AG-bound ribosome. We suggest that altering the conformations of ribosomal protein uL6 and rRNA helix H69, which interact with initiation-factor IF2, interferes with proper protein synthesis initiation.
关键词：ribosome ; antibiotic ; resistance ; aminoglycoside ; cystic fibrosis