ArticleNature structural & molecular biology2025
Structural basis of the mechanism and inhibition of a human ceramide synthase.
Article in Nature structural & molecular biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- The Batten disease protein CLN8 is a stereospecific acyltransferase in bis(monoacylglycero)phosphate biosynthesis.Nature cell biology · 2026Article
- Discovery of a potential CERS2 inhibitor: hit compound identification via structure-based virtual screening and molecular dynamics simulations.Molecular diversity · 2026Article
- Review
- Hypothalamic ceramide metabolism in obesity and dysregulation of glucose homeostasis.Reviews in endocrine & metabolic disorders · 2026Review
- Inhibition of ceramide synthesis ameliorates body wasting in a cancer cachexia model.The Journal of clinical investigation · 2026Article
- Structural and functional dissection of a higher-order oligomerization interface in yeast ceramide synthase.Nature communications · 2026Article
- Exploring Ceramide C16:0 as a Novel Biomarker and Therapeutic Target for Atherosclerosis.Journal of the American Heart Association · 2026Review
- Biliopancreatic diversion with duodenal switch improve polycystic ovary syndrome with decreased serum ceramides.Frontiers in endocrinology · 2026Article
- CERS6 promotes esophageal squamous cell carcinoma proliferation by increasing the stability of RPN1.Cell death discovery · 2025Article
- Proteomic Ligandability Maps of Phosphorus(V) Stereoprobes Identify Covalent TLCD1 Inhibitors.Journal of the American Chemical Society · 2025Article
- Structural basis of the mechanism and inhibition of a human ceramide synthase.Nature structural & molecular biology · 2025Article
- TRAM-LAG1-CLN8 family proteins are acyltransferases regulating phospholipid composition.Science advances · 2025Article
- Proteomic Ligandability Maps of Phosphorus(V) Stereoprobes Identify Covalent TLCD1 Inhibitors.bioRxiv : the preprint server for biology · 2025Article
- Don't Be Surprised When These Surprise You: Some Infrequently Studied Sphingoid Bases, Metabolites, and Factors That Should Be Kept in Mind During Sphingolipidomic Studies.International journal of molecular sciences · 2025Review
- Optical control of sphingolipid biosynthesis using photoswitchable sphingosines.Journal of lipid research · 2025Article
- Optical control of sphingolipid biosynthesis using photoswitchable sphingosines.Journal of lipid research · 2025Article
- Optical control of sphingolipid biosynthesis using photoswitchable sphingosines.bioRxiv : the preprint server for biology · 2024Article
- Fine-tuned protein-lipid interactions in biological membranes: exploration and implications of the ORMDL-ceramide negative feedback loop in the endoplasmic reticulum.Frontiers in cell and developmental biology · 2024Article
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Authors and funding
13 authors.
Funding
Abstract
Ceramides are bioactive sphingolipids crucial for regulating cellular metabolism. Ceramides and dihydroceramides are synthesized by six ceramide synthase (CerS) enzymes, each with specificity for different acyl-CoA substrates. Ceramide with a 16-carbon acyl chain (C16 ceramide) has been implicated in obesity, insulin resistance and liver disease and the C16 ceramide-synthesizing CerS6 is regarded as an attractive drug target for obesity-associated disease. Despite their importance, the molecular mechanism underlying ceramide synthesis by CerS enzymes remains poorly understood. Here we report cryo-electron microscopy structures of human CerS6, capturing covalent intermediate and product-bound states. These structures, along with biochemical characterization, reveal that CerS catalysis proceeds through a ping-pong reaction mechanism involving a covalent acyl-enzyme intermediate. Notably, the product-bound structure was obtained upon reaction with the mycotoxin fumonisin B1, yielding insights into its inhibition of CerS. These results provide a framework for understanding CerS function, selectivity and inhibition and open routes for future drug discovery.
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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.