ArticleProceedings of the National Academy of Sciences of the United States of America2012
Crystal structure of Enpp1, an extracellular glycoprotein involved in bone mineralization and insulin signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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Who cites it
87 citing papers in PubMed, 138 citations in OpenAlex.
- From initial complete response to recurrence: ENPP1 mutation drives cisplatin resistance through STING/NF-κB/IL-6 axis in hypopharyngeal squamous cell carcinoma.British journal of cancer · 2026Article
- Elastin calcification during the initial stage of vascular calcification in kl/kl mice is suppressed by the calcimimetic upacicalcet.Scientific reports · 2026Article
- A direct, real-time, spectrophotometric assay for measuring ENPP1-catalyzed cGAMP hydrolysis.The Journal of biological chemistry · 2026Article
- Modulating Galectin-1 in human osteoblast-like cells alters mineralisation and influences the expression of genes associated with osteoblasts and osteocytes.Bioscience reports · 2026Article
- Comprehensive analysis of differential mRNA, lncRNA and circRNA and their ceRNA network in the Longissimus Dorsi Muscle of Jerseyyak in response to dietary protein levels.Frontiers in veterinary science · 2026Article
- ENPP1 inhibitor with ultralong drug-target residence time as an innate immune checkpoint blockade cancer therapy.Cell reports. Medicine · 2025Article
- Physical and chemical niche of human growth plate for polarized bone development.Nature communications · 2025Article
- Phosphate in Physiological and Pathological Mineralization: Important yet Often Unheeded.MedComm · 2025Review
- Article
- Modulation of host ATP levels by secreted bacterial effectors.Nature communications · 2025Article
- Therapeutic approaches for the treatment of genetic and acquired cardiovascular calcification.Frontiers in cardiovascular medicine · 2025Review
- Impact of theFrontiers in endocrinology · 2025Article
- Role of ENPP1 in cancer pathogenesis: Mechanisms and clinical implications (Review).Oncology letters · 2024Review
- A humanized monoclonal antibody targeting an ectonucleotidase rescues cardiac metabolism and heart function after myocardial infarction.Cell reports. Medicine · 2024Article
- Homozygous splice-site variant in ENPP1 underlies generalized arterial calcification of infancy.BMC pediatrics · 2024Article
- Extracellular Purine Metabolism-Potential Target in Multiple Sclerosis.Molecular neurobiology · 2024Review
- Unveiling the molecular mechanisms of the type IX secretion system's response regulator: Structural and functional insights.PNAS nexus · 2024Article
- Review
- Structure-based virtual screening andMicrobiology spectrum · 2024Article
- Naturally occurring quercetin and myricetin as potent inhibitors for human ectonucleotide pyrophosphatase/phosphodiesterase 1.Scientific reports · 2024Article
27 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Enpp1 is a membrane-bound glycoprotein that regulates bone mineralization by hydrolyzing extracellular nucleotide triphosphates to produce pyrophosphate. Enpp1 dysfunction causes human diseases characterized by ectopic calcification. Enpp1 also inhibits insulin signaling, and an Enpp1 polymorphism is associated with insulin resistance. However, the precise mechanism by which Enpp1 functions in these cellular processes remains elusive. Here, we report the crystal structures of the extracellular region of mouse Enpp1 in complex with four different nucleotide monophosphates, at resolutions of 2.7-3.2 Å. The nucleotides are accommodated in a pocket formed by an insertion loop in the catalytic domain, explaining the preference of Enpp1 for an ATP substrate. Structural mapping of disease-associated mutations indicated the functional importance of the interdomain interactions. A structural comparison of Enpp1 with Enpp2, a lysophospholipase D, revealed marked differences in the domain arrangements and active-site architectures. Notably, the Enpp1 mutant lacking the insertion loop lost the nucleotide-hydrolyzing activity but instead gained the lysophospholipid-hydrolyzing activity of Enpp2. Our findings provide structural insights into how the Enpp family proteins evolved to exert their diverse cellular functions.
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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.