Structural basis for the recognition of peptide RJPXD33 by acyltransferases in lipid a biosynthesis

Abstract

Background: Peptide RJPXD33 binds to and inhibits both LpxA and LpxD acyltransferases. Results: The crystal structure of the antibacterial peptide RJPXD33 complexed to E. coli LpxA was determined. Conclusion: RJPXD33 binds to E. coli LpxA in a unique modality that mimics the (R)-β-hydroxyacyl pantetheine moiety of substrate acyl-ACP. Significance: Bioactive, dual binding LpxA/LpxD peptides raise the possibility of designing less resistance-prone peptidomimetics and/or small molecule antibacterials. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc. Published in the U.S.A.