ArticleNature structural & molecular biology2011
Structural basis of substrate discrimination and integrin binding by autotaxin.
Article in Nature structural & molecular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers.
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Who cites it
129 citing papers in PubMed, 279 citations in OpenAlex.
- The effects of aspirin and fish oil consumption on lysophosphatidylcholines and lysophosphatidic acids and their correlates with platelet aggregation in adults with diabetes mellitus.Prostaglandins, leukotrienes, and essential fatty acidsTrial
- An aerosolized dual-action autotaxin inhibitor-PPARγ agonist for the treatment of pulmonary fibrosis.Cell reports. Medicine · 2026Article
- Quantum Methods in Drug Discovery: An Introduction to the Theoceptor (Theoretical Receptor) Approach.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Pancreatic CAF-Derived Autotaxin Drives Autocrine CTGF Expression to Modulate Protumorigenic Signaling.Molecular cancer therapeutics · 2025Article
- Trends on Potential Boron-containing Drugs by Advancements in Ligand-protein Crystals Complexes.Current medicinal chemistry · 2025Review
- Review
- In situ serial crystallography facilitates 96-well plate structural analysis at low symmetry.IUCrJ · 2024Article
- From Classical to Alternative Pathways of 2-Arachidonoylglycerol Synthesis: AlterAGs at the Crossroad of Endocannabinoid and Lysophospholipid Signaling.Molecules (Basel, Switzerland) · 2024Review
- Unveiling the molecular mechanisms of the type IX secretion system's response regulator: Structural and functional insights.PNAS nexus · 2024Article
- Autotaxin-Lysophosphatidate Axis: Promoter of Cancer Development and Possible Therapeutic Implications.International journal of molecular sciences · 2024Review
- ENPP1 in Blood and Bone: Skeletal and Soft Tissue Diseases Induced by ENPP1 Deficiency.Annual review of pathology · 2024Review
- The autotaxin-LPA axis promotes membrane trafficking and secretion in yolk sac visceral endoderm cells.Biology open · 2023Article
- Recent Advancements of Aptamers in Cancer Therapy.ACS omega · 2023Review
- Autotaxin inhibitor IOA-289 reduces gastrointestinal cancer progression in preclinical models.Journal of experimental & clinical cancer research : CR · 2023Article
- Regulation of CD8 T-cell signaling, metabolism, and cytotoxic activity by extracellular lysophosphatidic acid.Immunological reviews · 2023Review
- Characterization and translational development of IOA-289, a novel autotaxin inhibitor for the treatment of solid tumors.Immuno-oncology technology · 2023Article
- Linking medicinal cannabis to autotaxin-lysophosphatidic acid signaling.Life science alliance · 2023Article
- Untargeted metabolomics to expand the chemical space of the marine diatomFrontiers in microbiology · 2023Article
- Lysophosphatidic acid signaling via LPAJournal of neurochemistry · 2022Article
- Review
69 more citing papers are in PubMed but not listed here.
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Authors and funding
24 authors at 6 institutions in 4 countries.
Funding
Abstract
Autotaxin (ATX, also known as ectonucleotide pyrophosphatase/phosphodiesterase-2, ENPP2) is a secreted lysophospholipase D that generates the lipid mediator lysophosphatidic acid (LPA), a mitogen and chemoattractant for many cell types. ATX-LPA signaling is involved in various pathologies including tumor progression and inflammation. However, the molecular basis of substrate recognition and catalysis by ATX and the mechanism by which it interacts with target cells are unclear. Here, we present the crystal structure of ATX, alone and in complex with a small-molecule inhibitor. We have identified a hydrophobic lipid-binding pocket and mapped key residues for catalysis and selection between nucleotide and phospholipid substrates. We have shown that ATX interacts with cell-surface integrins through its N-terminal somatomedin B-like domains, using an atypical mechanism. Our results define determinants of substrate discrimination by the ENPP family, suggest how ATX promotes localized LPA signaling and suggest new approaches for targeting ATX with small-molecule therapeutic agents.
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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.