ArticleThe Journal of biological chemistry2014
Molecular basis of purinergic signal metabolism by ectonucleotide pyrophosphatase/phosphodiesterases 4 and 1 and implications in stroke.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 49 citations in OpenAlex.
- A direct, real-time, spectrophotometric assay for measuring ENPP1-catalyzed cGAMP hydrolysis.The Journal of biological chemistry · 2026Article
- The lysosomal catabolism of nucleic acids-critical regulators of the innate immune system.Nucleic acids research · 2025Review
- Free amino acids accelerate the time-dependent inactivation of rat liver nucleotide pyrophosphatase/phosphodiesterase Enpp3 elicited by EDTA.Amino acids · 2024Article
- Review
- 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
- ENPP1 in Blood and Bone: Skeletal and Soft Tissue Diseases Induced by ENPP1 Deficiency.Annual review of pathology · 2024Review
- AlphaFill: enriching AlphaFold models with ligands and cofactors.Nature methods · 2023Article
- Human antibodies targeting ENPP1 as candidate therapeutics for cancers.Frontiers in immunology · 2023Article
- Purification, crystallization and crystallographic analysis of the PorX response regulator associated with the type IX secretion system.Acta crystallographica. Section F, Structural biology communications · 2022Article
- The enpp4 ectonucleotidase regulates kidney patterning signalling networks in Xenopus embryos.Communications biology · 2021Article
- Discovery of potent nucleotide pyrophosphatase/phosphodiesterase3 (NPP3) inhibitors with ancillary carbonic anhydrase inhibition for cancer (immuno)therapy.RSC medicinal chemistry · 2021Article
- Tanshinones induce tumor cell apoptosis via directly targeting FHIT.Scientific reports · 2021Article
- Sulfated Polysaccharides from Macroalgae Are Potent Dual Inhibitors of Human ATP-Hydrolyzing Ectonucleotidases NPP1 and CD39.Marine drugs · 2021Article
- Crystallization of ectonucleotide phosphodiesterase/pyrophosphatase-3 and orientation of the SMB domains in the full-length ectodomain.Acta crystallographica. Section F, Structural biology communications · 2018Article
- Increased ApPurinergic signalling · 2018Article
- Crystal structure and substrate binding mode of ectonucleotide phosphodiesterase/pyrophosphatase-3 (NPP3).Scientific reports · 2018Article
- Review
- Crystal structure of the human alkaline sphingomyelinase provides insights into substrate recognition.The Journal of biological chemistry · 2017Article
- Discovery and synthetic optimization of a novel scaffold for hydrophobic tunnel-targeted autotaxin inhibition.Bioorganic & medicinal chemistry · 2016Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
NPP4 is a type I extracellular membrane protein on brain vascular endothelium inducing platelet aggregation via the hydrolysis of Ap3A, whereas NPP1 is a type II extracellular membrane protein principally present on the surface of chondrocytes that regulates tissue mineralization. To understand the metabolism of purinergic signals resulting in the physiologic activities of the two enzymes, we report the high resolution crystal structure of human NPP4 and explore the molecular basis of its substrate specificity with NPP1. Both enzymes cleave Ap3A, but only NPP1 can hydrolyze ATP. Comparative structural analysis reveals a tripartite lysine claw in NPP1 that stabilizes the terminal phosphate of ATP, whereas the corresponding region of NPP4 contains features that hinder this binding orientation, thereby inhibiting ATP hydrolysis. Furthermore, we show that NPP1 is unable to induce platelet aggregation at physiologic concentrations reported in human blood, but it could stimulate platelet aggregation if localized at low nanomolar concentrations on vascular endothelium. The combined studies expand our understanding of NPP1 and NPP4 substrate specificity and range and provide a rational mechanism by which polymorphisms in NPP1 confer stroke resistance.
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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.