title: Three-dimensional solution structure of bottromycin A2: a potent antibiotic active against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci.
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.
authors.affiliation: School of Pharmacy, Kitasato University, 5–9–1 Shirokane, Minato-ku, Tokyo, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Gouda
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamada
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ideguchi
authors.forename: Akihiro
authors.initials: A
authors.lastname: Sugawara
authors.forename: Tomoyasu
authors.initials: T
authors.lastname: Hirose
authors.forename: Satoshi
authors.initials: S
authors.lastname: Omura
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Sunazuka
authors.forename: Shuichi
authors.initials: S
authors.lastname: Hirono
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D016983:Enterococcus / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008958:Models, Molecular; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology; D012996:Solutions / Q000737:chemistry; D020713:Vancomycin Resistance
chemical_list: D000900:Anti-Bacterial Agents; D010456:Peptides, Cyclic; D012996:Solutions; C012218:bottromycin A(2)