Rotational-Echo Double Resonance Characterization of Vancomycin Binding Sites in Staphylococcus aureus

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• 作者：Sung Joon Kim ; Lynette Cegelski ; Daniel R. Studelska ; Robert D. O'Connor ; Anil K. Mehta ; and Jacob Schaefer
• 刊名：Biochemistry
• 出版年：2002
• 出版时间：June 4, 2002
• 年：2002
• 卷：41
• 期：22
• 页码：6967 - 6977
• 全文大小：262K
• 年卷期：v.41,no.22(June 4, 2002)
• ISSN：1520-4995

文摘

Solid-state NMR experiments with stable isotope-labeled Staphylococcus aureus have providedinsight into the structure of the peptidoglycan binding site of a potent fluorobiphenyl derivative ofchloroeremomycin (Eli Lilly LY329332). Rotational-echo double resonance (REDOR) NMR providedinternuclear distances from the ¹⁹F of this glycopeptide antibiotic to natural-abundance ³¹P and to specific¹³C and ¹⁵N labels biosynthetically incorporated into the bacteria from labeled alanine, glycine, or lysinein the growth medium. Results from experiments with intact late log phase bacteria and cell walls indicatedhomogeneous drug-peptidoglycan binding. Drug dimers were not detected in situ, and the hydrophobicfluorobiphenyl group of LY329332 did not insert into the bilayer membrane. A model of the binding siteconsistent with the REDOR results positions the vancomycin cleft around an un-cross-linked D-Ala-D-Ala peptide stem with the fluorobiphenyl moiety of the antibiotic near the base of a second, proximatestem in a locally ordered peptidoglycan matrix.