ArticleProceedings of the National Academy of Sciences of the United States of America2018
Crystal structure of the mammalian lipopolysaccharide detoxifier.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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Who cites it
23 citing papers in PubMed, 32 citations in OpenAlex.
- Identification and characterization of a lipopolysaccharide binding, anti-inflammatory protein fromGut microbes · 2026Article
- Rapidly evolving aphid gall effector proteins exhibit saposin-like folds.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Rapidly evolving aphid gall effector proteins exhibit saposin-like folds.bioRxiv : the preprint server for biology · 2026Article
- Down-Regulation of Acyloxyacyl Hydrolase Expression in Alzheimer's Disease Impairs LPS Detoxification and Contributes to Brain Pro-Inflammatory Signaling.Molecules (Basel, Switzerland) · 2026Article
- Article
- Metabolic Endotoxemia: From the Gut to Neurodegeneration.International journal of molecular sciences · 2024Review
- Human Saposin B Ligand Binding and Presentation to α-Galactosidase A.bioRxiv : the preprint server for biology · 2024Article
- In Situ Neutralization and Detoxification of LPS to Attenuate Hyperinflammation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Catalytic site flexibility facilitates the substrate and catalytic promiscuity of Vibrio dual lipase/transferase.Nature communications · 2023Article
- Gut dysbiosis induces the development of mastitis through a reduction in host anti-inflammatory enzyme activity by endotoxemia.Microbiome · 2022Article
- Acyloxyacyl hydrolase deficiency induces chronic inflammation and bone loss in male mice.Journal of molecular medicine (Berlin, Germany) · 2022Article
- The influence of calcium ions (CaJCIS open · 2022Article
- Article
- Phospholipase activity of acyloxyacyl hydrolase induces IL-22-producing CD1a-autoreactive T cells in individuals with psoriasis.European journal of immunology · 2022Article
- Monocyte biology conserved across species: Functional insights from cattle.Frontiers in immunology · 2022Article
- A highly conserved host lipase deacylates oxidized phospholipids and ameliorates acute lung injury in mice.eLife · 2021Article
- CE16 acetylesterases: in silico analysis, catalytic machinery prediction and comparison with related SGNH hydrolases.3 Biotech · 2021Article
- TLR4 and CD14 trafficking and its influence on LPS-induced pro-inflammatory signaling.Cellular and molecular life sciences : CMLS · 2021Review
- Biochemical transformation of bacterial lipopolysaccharides by acyloxyacyl hydrolase reduces host injury and promotes recovery.The Journal of biological chemistry · 2020Review
- Cell Type- and Stimulation-Dependent Transcriptional Programs Regulated by Atg16L1 and Its Crohn's Disease Risk Variant T300A.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
LPS is a potent bacterial endotoxin that triggers the innate immune system. Proper recognition of LPS by pattern-recognition receptors requires a full complement of typically six acyl chains in the lipid portion. Acyloxyacyl hydrolase (AOAH) is a host enzyme that removes secondary (acyloxyacyl-linked) fatty acids from LPS, rendering it immunologically inert. This activity is critical for recovery from immune tolerance that follows Gram-negative infection. To understand the molecular mechanism of AOAH function, we determined its crystal structure and its complex with LPS. The substrate's lipid moiety is accommodated in a large hydrophobic pocket formed by the saposin and catalytic domains with a secondary acyl chain inserted into a narrow lateral hydrophobic tunnel at the active site. The enzyme establishes dispensable contacts with the phosphate groups of LPS but does not interact with its oligosaccharide portion. Proteolytic processing allows movement of an amphipathic helix possibly involved in substrate access at membranes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.