Domain requirement of moenomycin binding to bifunctional transglycosylases and development of high-throughput discovery of antibiotics
Resource
Proceedings of the National Academy of Science, 105(2), 431-436
Journal
Proceedings of the National Academy of Sciences
Pages
431-436
Date Issued
2008
Date
2008
Author(s)
Cheng, Ting-Jen Rachel
Sung, Ming-Ta
Liao, Hsin-Yu
Chang, Yi-Fan
Chen, Chia-Wei
Huang, Chia-Ying
Chou, Lien-Yang
Wu, Yen-Da
Chen, Yin-Hsuan
Cheng, Yih-Shyun E.
Wong, Chi-Huey
Ma, Che
Cheng, Wei-Chieh
Abstract
Moenomycin inhibits bacterial growth by blocking the transglycosylase activity of class A penicillin-binding proteins (PBPs), which are key enzymes in bacterial cell wall synthesis. We compared the binding affinities of moenomycin A with various truncated PBPs by using surface plasmon resonance analysis and found that the transmembrane domain is important for moenomycin binding. Full-length class A PBPs from 16 bacterial species were produced, and their binding activities showed a correlation with the antimicrobial activity of moenomycin against Enterococcus faecalis and Staphylococcus aureus. On the basis of these findings, a fluorescence anisotropy-based high-throughput assay was developed and used successfully for identification of transglycosylase inhibitors.
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