Three-dimensional solution structure of bottromycin A 2: A potent antibiotic active against methicillin-resistant Staphylococcus aureus and vancomycin- resistant Enterococci

Hiroaki Gouda, Yutaka Kobayashi, Takeshi Yamada, Tetsuya Ideguchi, Akihiro Sugawara, Tomoyasu Hirose, Satoshi Omura, Toshiaki Sunazuka, Shuichi Hirono

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

The three-dimensional (3D) structure of bottromycin A 2, a natural anti-methicillin-resistant Staphylococcus aureus (MRSA) and anti-vancomycin-resistant Enterococci (VRE) agent consisting of seven amino acids, has been investigated through NMR spectroscopy. On the basis of 57 experimental constraints, a total of 34 converged structures were obtained. The average pairwise atomic root mean square difference is 0.74±0.59 Å for all heavy atoms. The resulting structure indicates an interesting feature in that the three C-terminal residues of bottromycin A 2 fold back on the 12-membered cyclic skeleton made by the four N-terminal residues. Thus, MePro(2) and Thia-β-Ala-OMe(7), modification of which significantly affects the antibacterial activities of bottromycin A 2, are located on one side of its 3D structure. These distinct structural features might be important for the binding of bottromycin A 2 with the bacterial ribosome.

Original languageEnglish
Pages (from-to)169-171
Number of pages3
JournalChemical and Pharmaceutical Bulletin
Volume60
Issue number2
DOIs
Publication statusPublished - 2012
Externally publishedYes

Keywords

  • Antibiotic
  • Bottromycin A
  • Methicillin-resistant Staphylococcus aureus
  • NMR
  • Solution structure
  • Vancomycin-resistant Enterococci

ASJC Scopus subject areas

  • Chemistry(all)
  • Drug Discovery

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