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

doi:10.1248/cpb.60.169

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 journal › Article › peer-review

17 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 language	English
Pages (from-to)	169-171
Number of pages	3
Journal	Chemical and Pharmaceutical Bulletin
Volume	60
Issue number	2
DOIs	https://doi.org/10.1248/cpb.60.169
Publication status	Published - 2012
Externally published	Yes

Keywords

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

ASJC Scopus subject areas

Chemistry(all)
Drug Discovery

Access to Document

10.1248/cpb.60.169

Cite this

Gouda, H., Kobayashi, Y., Yamada, T., Ideguchi, T., Sugawara, A., Hirose, T., Omura, S., Sunazuka, T., & Hirono, S. (2012). Three-dimensional solution structure of bottromycin A ₂: A potent antibiotic active against methicillin-resistant Staphylococcus aureus and vancomycin- resistant Enterococci. Chemical and Pharmaceutical Bulletin, 60(2), 169-171. https://doi.org/10.1248/cpb.60.169

Three-dimensional solution structure of bottromycin A ₂ : A potent antibiotic active against methicillin-resistant Staphylococcus aureus and vancomycin- resistant Enterococci. / Gouda, Hiroaki; Kobayashi, Yutaka; Yamada, Takeshi et al.

In: Chemical and Pharmaceutical Bulletin, Vol. 60, No. 2, 2012, p. 169-171.

Research output: Contribution to journal › Article › peer-review

Gouda, H, Kobayashi, Y, Yamada, T, Ideguchi, T, Sugawara, A, Hirose, T, Omura, S, Sunazuka, T & Hirono, S 2012, 'Three-dimensional solution structure of bottromycin A ₂: A potent antibiotic active against methicillin-resistant Staphylococcus aureus and vancomycin- resistant Enterococci', Chemical and Pharmaceutical Bulletin, vol. 60, no. 2, pp. 169-171. https://doi.org/10.1248/cpb.60.169

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