ArticleNature communications2018
Structural basis for the activation of acid ceramidase.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 95 citations in OpenAlex.
- Fluorogenic Tissue-Based Assessment of Acid Ceramidase Activity.Bio-protocol · 2026Article
- Cepharanthine inhibits lysosomes and induces apoptosis in triple‑negative breast cancer cells.Molecular medicine reports · 2026Article
- PSAP Protects Against Acute Myocardial Ischemia-Reperfusion Injury by Promoting ASAH1-Mediated Ceramide Metabolism.Journal of cardiovascular translational research · 2026Article
- Acid ceramidase overactivity drives ceramide loss, leading to atopic dry skin and Th2-skewed immune polarization.The Journal of pathology · 2026Article
- Curcumin as a ceramide metabolism-targeting agent: Molecular mechanisms and therapeutic implications in cancer.Molecular biology reports · 2026Review
- The crystal structure of human transport and Golgi organization 2 homolog (TANGO2) suggests a cysteine N-terminal nucleophile (Ntn) hydrolase.Acta crystallographica. Section D, Structural biology · 2026Article
- Acid ceramidase ASAH1 is a key regulator of epidermal ceramide levels and composition.The Journal of biological chemistry · 2026Article
- The Crystal Structure of Human Transport and Golgi Organization 2 Homolog (TANGO2) Protein Reveals an αββα-Fold Arrangement.Proteins · 2026Article
- Distinct CSF lipidomic profiles are associated with five proteomic subtypes in patients with Alzheimer's disease.Molecular neurodegeneration advances · 2026Article
- A novel intronic variant in the ASAH1 gene enhances aberrant splicing, causing spinal muscular atrophy with progressive myoclonic epilepsy.Italian journal of pediatrics · 2025Article
- Altered levels of sphingolipid metabolites in serum of locally advanced rectal cancer patients: A pilot study.Journal of medical biochemistry · 2025Article
- Acid Ceramidase Deficiency: New Insights on SMA-PME Natural History, Biomarkers, andNeurology. Genetics · 2025Article
- Cardiac dysfunction and altered gene expression in acid ceramidase-deficient mice.American journal of physiology. Heart and circulatory physiology · 2025Article
- Clinical and Genetic Profiles of 5q- and Non-5q-Spinal Muscular Atrophy Diseases in Pediatric Patients.Genes · 2024Review
- The role of ceranib-2 and its nanoform on the decrease of telomerase levels in human non-small cell cancer.Molecular biology reports · 2024Article
- Identification of a NovelIranian journal of child neurology · 2024Article
- Acid ceramidase regulates innate immune memory.Cell reports · 2023Article
- Lipids as Emerging Biomarkers in Neurodegenerative Diseases.International journal of molecular sciences · 2023Review
- Acid Ceramidase Inhibitor LCL-805 Antagonizes Akt Signaling and Promotes Iron-Dependent Cell Death in Acute Myeloid Leukemia.Cancers · 2023Article
- Neutral ceramidase-active site inhibitor chemotypes and binding modes.Bioorganic chemistry · 2023Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acid ceramidase (aCDase, ASAH1) hydrolyzes lysosomal membrane ceramide into sphingosine, the backbone of all sphingolipids, to regulate many cellular processes. Abnormal function of aCDase leads to Farber disease, spinal muscular atrophy with progressive myoclonic epilepsy, and is associated with Alzheimer's, diabetes, and cancer. Here, we present crystal structures of mammalian aCDases in both proenzyme and autocleaved forms. In the proenzyme, the catalytic center is buried and protected from solvent. Autocleavage triggers a conformational change exposing a hydrophobic channel leading to the active site. Substrate modeling suggests distinct catalytic mechanisms for substrate hydrolysis versus autocleavage. A hydrophobic surface surrounding the substrate binding channel appears to be a site of membrane attachment where the enzyme accepts substrates facilitated by the accessory protein, saposin-D. Structural mapping of disease mutations reveals that most would destabilize the protein fold. These results will inform the rational design of aCDase inhibitors and recombinant aCDase for disease therapeutics.
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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.