Recombinant Salmonella schwarzengrund Prolipoprotein diacylglyceryl transferase (lgt)
Description
Introduction
Recombinant Salmonella Schwarzengrund Prolipoprotein Diacylglyceryl Transferase (Lgt) is a genetically engineered enzyme critical for bacterial lipoprotein biosynthesis. Lgt catalyzes the transfer of an sn-1,2-diacylglyceryl group from phosphatidylglycerol to the conserved cysteine residue in prolipoproteins, a process essential for membrane anchoring and lipoprotein maturation . This enzyme is a validated antibacterial target due to its role in maintaining outer membrane integrity and pathogenicity .
Enzyme Architecture
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Membrane Topology: Lgt is embedded in the inner membrane via seven transmembrane segments, with its N-terminus facing the periplasm and C-terminus oriented toward the cytoplasm .
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Conserved Motifs: The Lgt signature motif contains invariant residues (Y26, N146, G154) critical for enzymatic activity. Mutational studies show these residues are indispensable for diacylglyceryl transfer .
Key Residues and Mutational Analysis
Role in Bacterial Pathogenesis
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Membrane Integrity: Lgt depletion in E. coli causes outer membrane permeabilization, increasing susceptibility to serum killing and antibiotics like ciprofloxacin and aztreonam .
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Virulence Attenuation: S. Schwarzengrund strains lacking functional Lgt show reduced survival in host environments, highlighting its role in infection .
Inhibitor Development
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First-Generation Inhibitors: Macrocyclic compounds (e.g., G2823, G2824) inhibit E. coli Lgt in vitro (IC₅₀ = 0.5–2 µM) and exhibit bactericidal activity against multidrug-resistant Acinetobacter baumannii .
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Resistance Mechanisms: Unlike downstream lipoprotein pathway inhibitors (e.g., LspA-targeting globomycin), Lgt inhibitors remain effective even in lpp (major outer membrane lipoprotein) deletion strains .
Clinical and Biotechnological Relevance
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Antimicrobial Target: Lgt’s essentiality and conserved structure across Gram-negative bacteria make it a priority for novel antibiotic development .
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Diagnostic Use: Recombinant Lgt serves as an antigen for antibody production in serological assays to detect Salmonella infections .
Challenges and Future Directions
Product Specs
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Target Background
This recombinant Salmonella schwarzengrund Prolipoprotein diacylglyceryl transferase (Lgt) catalyzes the transfer of the diacylglyceryl group from phosphatidylglycerol to the sulfhydryl group of the N-terminal cysteine of a prolipoprotein. This is the initial step in mature lipoprotein formation.
KEGG: sew:SeSA_A3166
