ArticleThe Journal of biological chemistry2016
Crystal Structure of the Acid Sphingomyelinase-like Phosphodiesterase SMPDL3B Provides Insights into Determinants of Substrate Specificity.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
16 citing papers in PubMed, 22 citations in OpenAlex.
- Contribution of sphingomyelin phosphodiesterase acid-like 3B to the proliferation, migration, and invasion of ovarian cancer cells.Translational cancer research · 2024Article
- Molecular basis for the catalytic mechanism of human neutral sphingomyelinases 1 (hSMPD2).Nature communications · 2023Article
- Proteomic, Metabolomic, and Lipidomic Analyses of Lung Tissue Exposed to Mustard Gas.Metabolites · 2022Article
- Sphingomyelin Phodiesterase Acid-Like 3A Promotes Hepatocellular Carcinoma Growth Through the Enhancer of Rudimentary Homolog.Frontiers in oncology · 2022Article
- Podocyte Sphingolipid Signaling in Nephrotic Syndrome.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2021Review
- Macrophage-derived thrombospondin 1 promotes obesity-associated non-alcoholic fatty liver disease.JHEP reports : innovation in hepatology · 2021Article
- Intravital imaging of interactions between iNKT and kupffer cells to clear free lipids during steatohepatitis.Theranostics · 2021Article
- SMPDL3B Predicts Poor Prognosis and Contributes to Development of Acute Myeloid Leukemia.Frontiers in molecular biosciences · 2021Article
- Role of Sphingolipid Signaling in Glomerular Diseases: Focus on DKD and FSGS.Journal of cellular signaling · 2020Article
- Human alkaline ceramidase 2 promotes the growth, invasion, and migration of hepatocellular carcinoma cells via sphingomyelin phosphodiesterase acid-like 3B.Cancer science · 2020Article
- PhosphodiesteraseInternational journal of molecular sciences · 2020Article
- In vitro and bioinformatics mechanistic-based approach for cadmium carcinogenicity understanding.Toxicology in vitro : an international journal published in association with BIBRA · 2020Article
- iTRAQ-Based Quantitative Proteomic Analysis of Digestive Juice across the First 48 Hours of the Fifth Instar in Silkworm Larvae.International journal of molecular sciences · 2019Article
- Regulation of the amount of ceramide-1-phosphate synthesized in differentiated human podocytes.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2019Article
- SMPDL3b modulates insulin receptor signaling in diabetic kidney disease.Nature communications · 2019Article
- Sphingomyelin Breakdown in T Cells: Role of Membrane Compartmentalization in T Cell Signaling and Interference by a Pathogen.Frontiers in cell and developmental biology · 2019Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
The enzyme acid sphingomyelinase-like phosphodiesterase 3B (SMPDL3B) was shown to act as a negative regulator of innate immune signaling, affecting cellular lipid composition and membrane fluidity. Furthermore, several reports identified this enzyme as an off target of the therapeutic antibody rituximab, with implications in kidney disorders. However, structural information for this protein is lacking. Here we present the high resolution crystal structure of murine SMPDL3B, which reveals a substrate binding site strikingly different from its paralogs. The active site is located in a narrow boot-shaped cavity. We identify a unique loop near the active site that appears to impose size constraints on incoming substrates. A structure in complex with phosphocholine indicates that the protein recognizes this head group via an aromatic box, a typical choline-binding motif. Although a potential substrate for SMPDL3B is sphingomyelin, we identify other possible substrates such as CDP-choline, ATP, and ADP. Functional experiments employing structure-guided mutagenesis in macrophages highlight amino acid residues potentially involved in recognition of endogenous substrates. Our study is an important step toward elucidating the specific function of this poorly characterized enzyme.
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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.