Mapping of a lipoglycopeptide antibiotic binding site on Staphylococcus aureus penicillin-binding protein 2 using a vancomycin photoaffinity analogue

Nakamura, Jun; Ichikawa, Ryota; Yamashiro, Hidenori; Takasawa, Takafumi; Wang, Xaolei; Kawai, Yasushi; Xu, Shu; Maki, Hideki; Arimoto, Hirokazu

doi:10.1039/c2md20005h

Cited by 1 publication

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“…Transglycosylation of the radiolabeled depsi-lipid II by S. aureus PBP2 : By using the radiolabeled product of the MurG reaction, we next investigated the polymerization of peptidoglycan with purified S. aureus PBP2 enzyme. A full-length PBP2 of S. aureus RN4220 strain 29 , 30 was prepared as previously described. The C35-lipid II containing a d -Ala- d -Ala terminal was used for the vancomycin-susceptible model, and the C35-depsi-lipid II with a d -Ala- d -Lac terminal was used for the resistant model.…”

Section: Resultsmentioning

confidence: 99%

Staphylococcus aureus Penicillin‐Binding Protein 2 Can Use Depsi‐Lipid II Derived from Vancomycin‐Resistant Strains for Cell Wall Synthesis

Nakamura

Yamashiro

Miya

et al. 2013

Chemistry A European J

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Vancomycin-resistant Staphylococcus aureus (S. aureus) (VRSA) uses depsipeptide-containing modified cell-wall precursors for the biosynthesis of peptidoglycan. Transglycosylase is responsible for the polymerization of the peptidoglycan, and the penicillin-binding protein 2 (PBP2) plays a major role in the polymerization among several transglycosylases of wild-type S. aureus. However, it is unclear whether VRSA processes the depsipeptide-containing peptidoglycan precursor by using PBP2. Here, we describe the total synthesis of depsi-lipid I, a cell-wall precursor of VRSA. By using this chemistry, we prepared a depsi-lipid II analogue as substrate for a cell-free transglycosylation system. The reconstituted system revealed that the PBP2 of S. aureus is able to process a depsi-lipid II intermediate as efficiently as its normal substrate. Moreover, the system was successfully used to demonstrate the difference in the mode of action of the two antibiotics moenomycin and vancomycin.

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Section: Resultsmentioning

confidence: 99%