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Rethinking ramoplanin: the role of substrate binding in inhibition of peptidoglycan biosynthesis.

Authors
  • Helm, Jeremiah S
  • Chen, Lan
  • Walker, Suzanne
Type
Published Article
Journal
Journal of the American Chemical Society
Publication Date
Nov 27, 2002
Volume
124
Issue
47
Pages
13970–13971
Identifiers
PMID: 12440876
Source
Medline
License
Unknown

Abstract

Ramoplanin is a cyclicdepsipeptide antibiotic that inhibits peptidoglycan biosynthesis. It was proposed in 1990 to block the MurG step of peptidoglycan synthesis by binding to the substrate of MurG, Lipid I. The proposed mechanism of MurG inhibition has become widely accepted even though it was never directly tested. In this paper, we disprove the accepted mechanism for how ramoplanin functions, and we present an alternative mechanism. This work has implications for the design of ramoplanin derivatives and may influence how other proposed substrate binding antibiotics are studied.

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