ArticleNature communications2021
Nucleic acid binding by SAMHD1 contributes to the antiretroviral activity and is enhanced by the GpsN modification.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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Who cites it
25 citing papers in PubMed, 41 citations in OpenAlex.
- Allosteric targeting with antiviral nucleotide analogs allows fine-tuning of SAMHD1 dNTPase activity.The Journal of biological chemistry · 2026Article
- Selective depletion of tumor-associated SAMHD1 enhances chemotherapeutic efficacy and antitumor immune responses.Signal transduction and targeted therapy · 2025Article
- Reaction Mechanism and Metal Selectivity of Human SAMHD1 Elucidated by QM/MM Calculations.ACS catalysis · 2025Article
- dNTP depletion and beyond: the multifaceted nature of SAMHD1-mediated viral restriction.Journal of virology · 2025Review
- SAMHD1 shapes deoxynucleotide triphosphate homeostasis by interconnecting the depletion and biosynthesis of different dNTPs.Nature communications · 2025Article
- Aggravating mechanisms from COVID-19.Virology journal · 2024Review
- Article
- May I Help You with Your Coat? HIV-1 Capsid Uncoating and Reverse Transcription.International journal of molecular sciences · 2024Review
- Platform-directed allostery and quaternary structure dynamics of SAMHD1 catalysis.Nature communications · 2024Article
- Identification and evaluation of small-molecule inhibitors against the dNTPase SAMHD1 via a comprehensive screening funnel.iScience · 2024Article
- Guanine-containing ssDNA and RNA induce dimeric and tetrameric structural forms of SAMHD1.Nucleic acids research · 2023Article
- Functionally comparable but evolutionarily distinct nucleotide-targeting effectors help identify conserved paradigms across diverse immune systems.Nucleic acids research · 2023Article
- Deoxyguanosine-Linked Bifunctional Inhibitor of SAMHD1 dNTPase Activity and Nucleic Acid Binding.ACS chemical biology · 2023Article
- Protein oxidation increases SAMHD1 binding ssDNA via its regulatory site.Nucleic acids research · 2023Article
- Targeting SAMHD1: To overcome multiple anti-cancer drugs resistance in hematological malignancies.Genes & diseases · 2023Review
- Deficiency for SAMHD1 activates MDA5 in a cGAS/STING-dependent manner.The Journal of experimental medicine · 2023Article
- Editorial: Advances in host-pathogen interactions for diseases in animals and birds.Frontiers in veterinary science · 2023Article
- Sulforaphane Reduces SAMHD1 Phosphorylation To Protect Macrophages from HIV-1 Infection.Journal of virology · 2022Article
- SAMHD1 deacetylation by SIRT1 promotes DNA end resection by facilitating DNA binding at double-strand breaks.Nature communications · 2022Article
- Targeting the DNA damage response and repair in cancer through nucleotide metabolism.Molecular oncology · 2022Review
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
SAMHD1 impedes infection of myeloid cells and resting T lymphocytes by retroviruses, and the enzymatic activity of the protein-dephosphorylation of deoxynucleotide triphosphates (dNTPs)-implicates enzymatic dNTP depletion in innate antiviral immunity. Here we show that the allosteric binding sites of the enzyme are plastic and can accommodate oligonucleotides in place of the allosteric activators, GTP and dNTP. SAMHD1 displays a preference for oligonucleotides containing phosphorothioate bonds in the Rp configuration located 3' to G nucleotides (GpsN), the modification pattern that occurs in a mechanism of antiviral defense in prokaryotes. In the presence of GTP and dNTPs, binding of GpsN-containing oligonucleotides promotes formation of a distinct tetramer with mixed occupancy of the allosteric sites. Mutations that impair formation of the mixed-occupancy complex abolish the antiretroviral activity of SAMHD1, but not its ability to deplete dNTPs. The findings link nucleic acid binding to the antiretroviral activity of SAMHD1, shed light on the immunomodulatory effects of synthetic phosphorothioated oligonucleotides and raise questions about the role of nucleic acid phosphorothioation in human innate immunity.
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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.