Download MendeleyAntimicrobial lipopeptide tridecaptin A1 selectively binds to Gram-negative lipid II.
Cochrane, S.A., Findlay, B., Bakhtiary, A., Acedo, J.Z., Rodriguez-Lopez, E.M., Mercier, P., Vederas, J.C.(2016) Proc Natl Acad Sci U S A 113: 11561-11566
- PubMed: 27688760
- DOI: https://doi.org/10.1073/pnas.1608623113
- Primary Citation of Related Structures:
2N5W, 2N5Y - PubMed Abstract:
Tridecaptin A 1 (TriA 1 ) is a nonribosomal lipopeptide with selective antimicrobial activity against Gram-negative bacteria. Here we show that TriA 1 exerts its bactericidal effect by binding to the bacterial cell-wall precursor lipid II on the inner membrane, disrupting the proton motive force. Biochemical and biophysical assays show that binding to the Gram-negative variant of lipid II is required for membrane disruption and that only the proton gradient is dispersed. The NMR solution structure of TriA 1 in dodecylphosphocholine micelles with lipid II has been determined, and molecular modeling was used to provide a structural model of the TriA 1 -lipid II complex. These results suggest that TriA 1 kills Gram-negative bacteria by a mechanism of action using a lipid-II-binding motif.
Organizational Affiliation:
Department of Chemistry, University of Alberta, Edmonton, AB, Canada T6G 2G2.
