ArticleNature communications2025
SAMHD1 shapes deoxynucleotide triphosphate homeostasis by interconnecting the depletion and biosynthesis of different dNTPs.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Nucleotide metabolic reprogramming: a "double-edged sword" in obesity-related inflammation-from metabolic adaptation to pathological imbalance.Journal of physiology and biochemistry · 2026Review
- Transition Metal Activation Reframes SAMHD1 Regulation.ACS chemical biology · 2026Article
- Transition metal activation reframes SAMHD1 regulation.bioRxiv : the preprint server for biology · 2026Article
- Allosteric targeting with antiviral nucleotide analogs allows fine-tuning of SAMHD1 dNTPase activity.The Journal of biological chemistry · 2026Article
- IMPDH inhibition enhances cytarabine efficacy in SAMHD1-expressing leukaemia cells via guanine nucleotide depletion.Molecular oncology · 2026Article
- Enhancing the Nucleoside Analog Response with Translational Therapeutic Approaches to Overcome Resistance.Cells · 2026Review
- Host restriction factors and p17-Driven inflammaging in HIV-1: From molecular pathogenesis to functional cure.AIMS microbiology · 2026Review
- Continuous assay for the dNTP triphosphohydrolase of activated SAMHD1.Analytical biochemistry · 2026Article
- Hepatocyte SAMHD1 Deficiency Attenuates Hepatic Steatosis via Suppression of SREBP Activation in a Mouse Model of Metabolic-Associated Steatotic Liver Disease.International journal of biological sciences · 2026Article
- dNTP depletion and beyond: the multifaceted nature of SAMHD1-mediated viral restriction.Journal of virology · 2025Review
- RRM2B deficiency causes dATP and dGTP depletion through enhanced degradation and slower synthesis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Insight into the genetics of a novel white-striped leaf in rice.Frontiers in plant science · 2025Article
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Abstract
SAMHD1 is a dNTPase that impedes replication of HIV-1 in myeloid cells and resting T lymphocytes. Here we elucidate the substrate activation mechanism of SAMHD1, which involves dNTP binding at allosteric sites and transient tetramerization. Our findings reveal that tetramerization alone is insufficient to promote dNTP hydrolysis; instead, the activation mechanism requires an inactive tetrameric intermediate with partially occupied allosteric sites. The equilibrium between inactive and active tetrameric states regulates dNTPase activity, driven by the binding and dissociation of additional allosteric dNTP ligands to the preassembled tetramer. Furthermore, catalytic efficiency, but not substrate specificity, is modulated by the identity of the dNTPs occupying the allosteric sites. We show how this allosteric regulation shapes deoxynucleotide homeostasis by balancing dNTP production and SAMHD1-catalyzed depletion. Notably, SAMHD1 exhibits a distinct functionality, which we term facilitated dNTP depletion, whereby increased biosynthesis of certain dNTPs enhances the depletion of others. The regulatory relationship between the biosynthesis and depletion of different dNTPs sheds light on the emerging role of SAMHD1 in the biology of dNTP homeostasis with implications for HIV/AIDS, innate antiviral immunity, T cell disorders, telomere maintenance and therapeutic efficacy of nucleoside analogs.
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