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  • 标题:The molecular basis of vancomycin resistance in clinically relevant Enterococci: Crystal structure of d-alanyl-d-lactate ligase (VanA)
  • 本地全文:下载
  • 作者:David I. Roper ; Trevor Huyton ; Alexei Vagin
  • 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:2000
  • 卷号:97
  • 期号:16
  • 页码:8921-8925
  • DOI:10.1073/pnas.150116497
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:D-alanine-D-lactate ligase from Enterococcus faecium BM4147 is directly responsible for the biosynthesis of alternate cell-wall precursors in bacteria, which are resistant to the glycopeptide antibiotic vancomycin. The crystal structure has been determined with data extending to 2.5-A resolution. This structure shows that the active site has unexpected interactions and is distinct from previous models for D-alanyl-D-lactate ligase mechanistic studies. It appears that the preference of the enzyme for lactate as a ligand over D-alanine could be mediated by electrostatic effects and/or a hydrogen-bonding network, which principally involve His-244. The structure of D-alanyl-D-lactate ligase provides a revised interpretation of the molecular events that lead to vancomycin resistance.
  • 关键词:x-ray crystal structure
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