ArticleThe Journal of biological chemistry2014
Allosteric regulation of the human and mouse deoxyribonucleotide triphosphohydrolase sterile α-motif/histidine-aspartate domain-containing protein 1 (SAMHD1).
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 24 papers.
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Who cites it
24 citing papers in PubMed, 33 citations in OpenAlex.
- Continuous assay for the dNTP triphosphohydrolase of activated SAMHD1.Analytical biochemistry · 2026Article
- A deoxynucleoside triphosphate triphosphohydrolase promotes cell cycle progression inJournal of bacteriology · 2025Article
- Prime Editing in Dividing and Quiescent Cells.International journal of molecular sciences · 2025Review
- SAMHD1 restricts the deoxyguanosine triphosphate pool contributing to telomere stability in telomerase-positive cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- Still no Rest for the Reductases: Ribonucleotide Reductase (RNR) Structure and Function: An Update.Sub-cellular biochemistry · 2022Review
- DCTPP1 prevents a mutator phenotype through the modulation of dCTP, dTTP and dUTP pools.Cellular and molecular life sciences : CMLS · 2020Article
- Purine-Metabolising Enzymes and Apoptosis in Cancer.Cancers · 2019Review
- The missing link: allostery and catalysis in the anti-viral protein SAMHD1.Biochemical Society transactions · 2019Review
- Dendritic Cells, the Double Agent in the War Against HIV-1.Frontiers in immunology · 2019Review
- The structural basis for cancer drug interactions with the catalytic and allosteric sites of SAMHD1.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- SAMHD1: Recurring roles in cell cycle, viral restriction, cancer, and innate immunity.Autoimmunity · 2018Review
- The SAM domain of mouse SAMHD1 is critical for its activation and regulation.Nature communications · 2018Article
- Substrates and Inhibitors of SAMHD1.PloS one · 2017Article
- The Dynamic Interplay between HIV-1, SAMHD1, and the Innate Antiviral Response.Frontiers in immunology · 2017Review
- Substrate Specificity of SAMHD1 Triphosphohydrolase Activity Is Controlled by Deoxyribonucleoside Triphosphates and Phosphorylation at Thr592.Biochemistry · 2016Article
- Functional organization of human SAMHD1 and mechanisms of HIV-1 restriction.Biological chemistry · 2016Review
- A continuous spectrophotometric enzyme-coupled assay for deoxynucleoside triphosphate triphosphohydrolases.Analytical biochemistry · 2016Article
- The Deoxynucleoside Triphosphate Triphosphohydrolase Activity of SAMHD1 Protein Contributes to the Mitochondrial DNA Depletion Associated with Genetic Deficiency of Deoxyguanosine Kinase.The Journal of biological chemistry · 2015Article
- Deoxyribonucleotide metabolism, mutagenesis and cancer.Nature reviews. Cancer · 2015Review
- SAMHD1 is a single-stranded nucleic acid binding protein with no active site-associated nuclease activity.Nucleic acids research · 2015Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The deoxyribonucleotide triphosphohydrolase SAMHD1 restricts lentiviral infection by depleting the dNTPs required for viral DNA synthesis. In cultured human fibroblasts SAMHD1 is expressed maximally during quiescence preventing accumulation of dNTPs outside S phase. siRNA silencing of SAMHD1 increases dNTP pools, stops cycling human cells in G1, and blocks DNA replication. Surprisingly, knock-out of the mouse gene does not affect the well being of the animals. dNTPs are both substrates and allosteric effectors for SAMHD1. In the crystal structure each subunit of the homotetrameric protein contains one substrate-binding site and two nonidentical effector-binding sites, site 1 binding dGTP, site 2 dGTP or dATP. Here we compare allosteric properties of pure recombinant human and mouse SAMHD1. Both enzymes are activated 3-4-fold by allosteric effectors. We propose that in quiescent cells where SAMHD1 is maximally expressed GTP binds to site 1 with very high affinity, stabilizing site 2 of the tetrameric structure. Any canonical dNTP can bind to site 2 and activate SAMHD1, but in cells only dATP or dTTP are present at sufficient concentrations. The apparent Km for dATP at site 2 is ∼10 μm for mouse and 1 μm for human SAMHD1, for dTTP the corresponding values are 50 and 2 μm. Tetrameric SAMHD1 is activated for the hydrolysis of any dNTP only after binding of a dNTP to site 2. The lower Km constants for human SAMHD1 induce activation at lower cellular concentrations of dNTPs thereby limiting the size of dNTP pools more efficiently in quiescent human cells.
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Registered trials
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