Domain Requirement of Moenomycin Binding to Bifunctional Transglycosylases and Development of High-throughput Discovery of Antibiotics

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2008 Jan 10

PMID 18182485

Citations 19

Authors

Ting-Jen Rachel Cheng

Ming-Ta Sung

Hsin-Yu Liao

Yi-Fan Chang

Chia-Wei Chen

Chia-Ying Huang

Lien-Yang Chou

Yen-Da Wu

Yin-Hsuan Chen

Yih-Shyun E Cheng

Chi-Huey Wong

Che Ma

Wei-Chieh Cheng

Affiliations

Soon will be listed here.

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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