ArticleBiochemistry2008
Purification and mutagenesis of LpxL, the lauroyltransferase of Escherichia coli lipid A biosynthesis.
Article in Biochemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 47 citations in OpenAlex.
- Structure and function of Salmonella inner membrane.Archives of microbiology · 2026Review
- Deep Sequencing of Crohn's Disease Lamina Propria Phagocytes Identifies Pathobionts and Correlates With Pro-Inflammatory Gene Expression.Inflammatory bowel diseases · 2025Article
- Preclinical safety and efficacy characterization of an LpxC inhibitor against Gram-negative pathogens.Science translational medicine · 2023Article
- Proteome level analysis of drug-resistantFrontiers in microbiology · 2023Article
- Hyperproduction of PHA copolymers containing high fractions of 4-hydroxybutyrate (4HB) by outer membrane-defected Halomonas bluephagenesis grown in bioreactors.Microbial biotechnology · 2022Article
- Article
- Development, Phenotypic Characterization and Genomic Analysis of aFrontiers in microbiology · 2021Article
- Metabolic phospholipid labeling of intact bacteria enables a fluorescence assay that detects compromised outer membranes.Journal of lipid research · 2020Article
- Article
- Current Progress in the Structural and Biochemical Characterization of Proteins Involved in the Assembly of Lipopolysaccharide.International journal of microbiology · 2018Review
- AlmG, responsible for polymyxin resistance in pandemicThe Journal of biological chemistry · 2017Article
- Molecular characterization and verification of azido-3,8-dideoxy-d-The Journal of biological chemistry · 2017Article
- Elucidation of salicylate attachment in celesticetin biosynthesis opens the door to create a library of more efficient hybrid lincosamide antibiotics.Chemical science · 2017Article
- Identification of Two Genes Encoding for the Late Acyltransferases of Lipid A in Klebsiella pneumoniae.Current microbiology · 2016Article
- Structure-guided enzymology of the lipid A acyltransferase LpxM reveals a dual activity mechanism.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Unique lipid anchor attaches Vi antigen capsule to the surface of Salmonella enterica serovar Typhi.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Article
- Influence of lipid A acylation pattern on membrane permeability and innate immune stimulation.Marine drugs · 2013Article
- Acyltransferases in bacteria.Microbiology and molecular biology reviews : MMBR · 2013Review
- Mechanistic characterization of the tetraacyldisaccharide-1-phosphate 4'-kinase LpxK involved in lipid A biosynthesis.Biochemistry · 2013Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Escherichia coli lipid A is a hexaacylated disaccharide of glucosamine with secondary laurate and myristate chains on the distal unit. Hexaacylated lipid A is a potent agonist of human Toll-like receptor 4, whereas its tetra- and pentaacylated precursors are antagonists. The inner membrane enzyme LpxL transfers laurate from lauroyl-acyl carrier protein to the 2'- R-3-hydroxymyristate moiety of the tetraacylated lipid A precursor Kdo 2-lipid IV A. LpxL has now been overexpressed, solubilized with n-dodecyl beta- d-maltopyranoside (DDM), and purified to homogeneity. LpxL migration on a gel filtration column is consistent with a molecular mass of 80 kDa, suggestive of an LpxL monomer (36 kDa) embedded in a DDM micelle. Mass spectrometry showed that deformylated LpxL was the predominant species, noncovalently bound to as many as 12 DDM molecules. Purified LpxL catalyzed not only the formation in vitro of Kdo 2-(lauroyl)-lipid IV A but also a slow second acylation, generating Kdo 2-(dilauroyl)-lipid IV A. Consistent with the Kdo dependence of crude LpxL in membranes, Kdo 2-lipid IV A is preferred 6000-fold over lipid IV A by the pure enzyme. Sequence comparisons suggest that LpxL shares distant homology with the glycerol-3-phosphate acyltransferase (GPAT) family, including a putative catalytic dyad located in a conserved H(X) 4D/E motif. Mutation of H132 or E137 to alanine reduces specific activity by over 3 orders of magnitude. Like many GPATs, LpxL can also utilize acyl-CoA as an alternative acyl donor, albeit at a slower rate. Our results show that the acyltransferases that generate the secondary acyl chains of lipid A are members of the GPAT family and set the stage for structural studies.
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