Target intelligence / Profile preview

Localization of lipoprotein CDE complex (LolCDE)

Target
LolCDE
Molecular classification
ABC transporter, Type VII ABC transporter, Transporter, Membrane protein complex
01

Overview

The LolCDE complex is an essential ATP-binding cassette (ABC) transporter located in the inner membrane of Gram-negative bacteria. It functions as the primary engine for the localization of lipoprotein (Lol) pathway, which is responsible for the transport of lipoproteins from their site of synthesis in the inner membrane to the outer membrane [1, 3]. The complex, typically composed of the transmembrane subunits LolC and LolE and the ATPase subunit LolD, specifically recognizes mature triacylated lipoproteins and utilizes ATP hydrolysis to extract them from the membrane [2, 14]. Once extracted, these lipoproteins are transferred to the periplasmic chaperone LolA for further trafficking to the outer membrane [1, 18]. Because the LolCDE system is vital for maintaining the structural integrity of the bacterial cell envelope and is highly conserved among Gram-negative pathogens but absent in humans, it represents a promising target for novel antimicrobial agents [6, 9]. Recent advancements have led to the discovery of inhibitors like lolamicin and G0507, which selectively block this transport process, causing lethal mislocalization of lipoproteins and providing a potential strategy to combat multidrug-resistant infections while sparing beneficial gut microbiota [8, 19].

Other names
LolCDE complexLolCDE ABC transporterLipoprotein-releasing ABC transporterLolCDE machineryLocalization of lipoprotein (Lol) system
02

Mechanism of action

Inhibition of lipoprotein extraction from the inner membrane by competitive binding to the LolCDE complex, leading to the toxic accumulation of lipoproteins in the inner membrane and subsequent bacterial cell death [7, 8, 11].

03

Biological functions

Lipoprotein transportOuter membrane biogenesisCell envelope maintenanceATP-dependent protein extractionBacterial cell wall homeostasis
04

Disease associations

Gram-negative bacterial infectionAntimicrobial resistance
05

Safety considerations

Development of resistance through target mutations in lolC, lolD, or lolE genesNarrow spectrum of activity limited to Gram-negative bacteriaPotential for rapid emergence of resistance in clinical settings
06

Interacting drugs

Lolamicin

3 more in the full profile.

07

Biomarkers

σE stress response inductionInner membrane accumulation of Lpp (murein lipoprotein)Bacterial growth inhibitionOuter membrane integrity defects

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