首页    期刊浏览 2024年11月08日 星期五
登录注册

文章基本信息

  • 标题:Structures of the orthosomycin antibiotics avilamycin and evernimicin in complex with the bacterial 70S ribosome
  • 本地全文:下载
  • 作者:Stefan Arenz ; Manuel F. Juette ; Michael Graf
  • 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:2016
  • 卷号:113
  • 期号:27
  • 页码:7527-7532
  • DOI:10.1073/pnas.1604790113
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:The ribosome is one of the major targets for therapeutic antibiotics; however, the rise in multidrug resistance is a growing threat to the utility of our current arsenal. The orthosomycin antibiotics evernimicin (EVN) and avilamycin (AVI) target the ribosome and do not display cross-resistance with any other classes of antibiotics, suggesting that they bind to a unique site on the ribosome and may therefore represent an avenue for development of new antimicrobial agents. Here we present cryo-EM structures of EVN and AVI in complex with the Escherichia coli ribosome at 3.6- to 3.9-Å resolution. The structures reveal that EVN and AVI bind to a single site on the large subunit that is distinct from other known antibiotic binding sites on the ribosome. Both antibiotics adopt an extended conformation spanning the minor grooves of helices 89 and 91 of the 23S rRNA and interacting with arginine residues of ribosomal protein L16. This binding site overlaps with the elbow region of A-site bound tRNA. Consistent with this finding, single-molecule FRET (smFRET) experiments show that both antibiotics interfere with late steps in the accommodation process, wherein aminoacyl-tRNA enters the peptidyltransferase center of the large ribosomal subunit. These data provide a structural and mechanistic rationale for how these antibiotics inhibit the elongation phase of protein synthesis.
  • 关键词:antimicrobial ; cryo-EM ; everninomicin ; rRNA ; Ziracin
国家哲学社会科学文献中心版权所有