Dataset Information

A Peptidomimetic Antibiotic Interacts with the Periplasmic Domain of LptD from Pseudomonas aeruginosa

ABSTRACT: Gram-negative bacterial infections are causing increasing levels of morbidity due to the rise of resistance to established antibiotics. New antibiotic classes with distinct molecular mode of action are therefore required. Recently, a family of macrocyclic peptidomimetics was discovered that target the outer membrane LPS transport protein LptD to specifically inhibit bacterial growth in Pseudomonas spp. To characterize the interaction of these antibiotics with LptD from P. aeruginosa, we combined photo-crosslinkable peptidomimetics and hypothesis-free mass spectrometry-based proteomics. We provide evidence that the antibiotic cross-links to the periplasmic segment of LptD, containing a ß-jellyroll domain and an N-terminal insert domain that is characteristic of Pseudomonas spp. Binding of the antibiotic to the periplasmic segment of LptD is expected to block LPS transport, consistent with the proposed mode of action and observed specificity of these antibiotics. These insights may prove valuable for the discovery of new antibiotics targeting the LPS transport pathway in other Gram-negative bacteria.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Pseudomonas Aeruginosa Pao1

SUBMITTER: Maik Müller

LAB HEAD: Bernd Wollscheid

PROVIDER: PXD008577 | Pride | 2018-06-21

REPOSITORIES: Pride

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A Peptidomimetic Antibiotic Interacts with the Periplasmic Domain of LptD from Pseudomonas aeruginosa.

Andolina Gloria G Bencze László-Csaba LC Zerbe Katja K Müller Maik M Steinmann Jessica J Kocherla Harsha H Mondal Milon M Sobek Jens J Moehle Kerstin K Malojčić Goran G Wollscheid Bernd B Robinson John A JA

ACS chemical biology 20180123 3

The outer membrane (OM) in Gram-negative bacteria is an asymmetric bilayer with mostly lipopolysaccharide (LPS) molecules in the outer leaflet. During OM biogenesis, new LPS molecules are transported from their site of assembly on the inner membrane to the OM by seven LPS transport proteins (LptA-G). The complex formed between the integral β-barrel OM protein LptD and the lipoprotein LptE is responsible for transporting LPS from the periplasmic side of the OM to its final location on the cell su ...[more]

PMID: 29359918

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			Action	DRS
	DDA_LptDE_lab_mix.raw	Raw
	DDA_LptDE_unlab_mix.raw	Raw
	DIA_LptDE_lab_r1.raw	Raw
	DIA_LptDE_lab_r2.raw	Raw
	DIA_LptDE_lab_r3.raw	Raw