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gc tp  (Jena Bioscience)


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    Structured Review

    Jena Bioscience gc tp
    Acyclovir-triphosphate (Ac-TP) and ganciclovir-triphosphate <t>(Gc-TP)</t> are allosteric site 1 (AS1) activators that differentially activate dNTP hydrolysis . A , rationale of the enzymatic assay. SAMHD1 is incubated with test compounds (100 μM, compounds: GTP (AS1-activator), dGTP (AS1-/AS2-activator/substrate), and dATP (AS2-activator/substrate). B , SAMHD1 was incubated with different combinations of activators/substrates/buffer (indicated by color ) and test compounds ( left ) in the enzyme-coupled assay. SAMHD1 activity normalized to buffer + dGTP (100 μM) control. Bars indicate means of three independent experiments, where dots represent individual values of technical duplicates. Error bars indicate SD. C , SAMHD1 was incubated with varying concentrations of GTP, Ac-TP, or Gc-TP and 100 μM of the indicated dNTP in the enzyme-coupled assay. SAMHD1 activity was normalized to dATP (100 μM) + GTP (100 μM) control. Data points indicate the mean of two independent experiments; each performed with technical duplicates; error bars indicate SD. SAMHD1, SAM and HD domain–containing protein 1. " width="250" height="auto" />
    Gc Tp, supplied by Jena Bioscience, used in various techniques. Bioz Stars score: 94/100, based on 5 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/product/gc+tp/Ganciclovir-triphosphate/pmc12934318-205-2-14
    Average 94 stars, based on 5 article reviews
    gc tp - by Bioz Stars, 2026-09
    94/100 stars

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    1) Product Images from "Allosteric targeting with antiviral nucleotide analogs allows fine-tuning of SAMHD1 dNTPase activity"

    Article Title: Allosteric targeting with antiviral nucleotide analogs allows fine-tuning of SAMHD1 dNTPase activity

    Journal: The Journal of Biological Chemistry

    doi: 10.1016/j.jbc.2026.111214

    Acyclovir-triphosphate (Ac-TP) and ganciclovir-triphosphate (Gc-TP) are allosteric site 1 (AS1) activators that differentially activate dNTP hydrolysis . A , rationale of the enzymatic assay. SAMHD1 is incubated with test compounds (100 μM,
    Figure Legend Snippet: Acyclovir-triphosphate (Ac-TP) and ganciclovir-triphosphate (Gc-TP) are allosteric site 1 (AS1) activators that differentially activate dNTP hydrolysis . A , rationale of the enzymatic assay. SAMHD1 is incubated with test compounds (100 μM, "X") and allosteric activators, substrates, or buffer (indicated by color ), allowing determination of where test compounds bind. Control compounds: GTP (AS1-activator), dGTP (AS1-/AS2-activator/substrate), and dATP (AS2-activator/substrate). B , SAMHD1 was incubated with different combinations of activators/substrates/buffer (indicated by color ) and test compounds ( left ) in the enzyme-coupled assay. SAMHD1 activity normalized to buffer + dGTP (100 μM) control. Bars indicate means of three independent experiments, where dots represent individual values of technical duplicates. Error bars indicate SD. C , SAMHD1 was incubated with varying concentrations of GTP, Ac-TP, or Gc-TP and 100 μM of the indicated dNTP in the enzyme-coupled assay. SAMHD1 activity was normalized to dATP (100 μM) + GTP (100 μM) control. Data points indicate the mean of two independent experiments; each performed with technical duplicates; error bars indicate SD. SAMHD1, SAM and HD domain–containing protein 1.

    Techniques Used: Enzymatic Assay, Incubation, Control, Activity Assay

    Acyclovir-triphosphate (Ac-TP) and ganciclovir-triphosphate (Gc-TP) bind to allosteric site 1 (AS1) and induce tetramerization . A , schematic of the AS1 competitive binding assay using the environmentally sensitive mant-GTP probe. As mant-GTP is displaced from AS1 by competitors, fluorescence signal decreases. B , SAMHD1 (2 μM) and mant-GTP (0.5 μM) were incubated with varying concentrations of AS1 competitors. Data points indicate means of three independent experiments; each performed with technical duplicates. No-compound controls for each competitor dilution series were considered as shared technical replicates (N = 6). Error bars indicate SD. p K i values ± SD were calculated from a competitive binding equation (see the section). ANOVA shows significant differences between p K i values for the three AS1 competitors ( p = 0.0007). Results of a post hoc Tukey’s multiple comparisons are indicated by asterisks , where ∗∗∗ and ∗∗ indicate adjusted p values ≤0.001 and ≤0.01, respectively. GTP versus Ac-TP: adjusted p = 0.0006; GTP versus Gc-TP: adjusted p = 0.0041; and Ac-TP versus Gc-TP: adjusted p = 0.1331. C , mass photometry quantification of SAMHD1 oligomeric states (monomer: M, dimer: D, and tetramer: T) after incubation with AS2 activator dATP (250 μM) and increasing concentrations of either GTP, Ac-TP, or Gc-TP between 0 and 1200 μM. Data shown are representative of three independent experiments. D , quantification of relative abundance of monomer, dimer, and tetramer oligomeric states as seen in C . Intensities are grouped by oligomeric state, and colors indicate different AS1 activators. Data points indicate means of three independent experiments; error bars indicate SD. mant-GTP, 2'/3′-O- N -methyl-anthraniloyl)-GTP; SAMHD1, SAM and HD domain–containing protein 1.
    Figure Legend Snippet: Acyclovir-triphosphate (Ac-TP) and ganciclovir-triphosphate (Gc-TP) bind to allosteric site 1 (AS1) and induce tetramerization . A , schematic of the AS1 competitive binding assay using the environmentally sensitive mant-GTP probe. As mant-GTP is displaced from AS1 by competitors, fluorescence signal decreases. B , SAMHD1 (2 μM) and mant-GTP (0.5 μM) were incubated with varying concentrations of AS1 competitors. Data points indicate means of three independent experiments; each performed with technical duplicates. No-compound controls for each competitor dilution series were considered as shared technical replicates (N = 6). Error bars indicate SD. p K i values ± SD were calculated from a competitive binding equation (see the section). ANOVA shows significant differences between p K i values for the three AS1 competitors ( p = 0.0007). Results of a post hoc Tukey’s multiple comparisons are indicated by asterisks , where ∗∗∗ and ∗∗ indicate adjusted p values ≤0.001 and ≤0.01, respectively. GTP versus Ac-TP: adjusted p = 0.0006; GTP versus Gc-TP: adjusted p = 0.0041; and Ac-TP versus Gc-TP: adjusted p = 0.1331. C , mass photometry quantification of SAMHD1 oligomeric states (monomer: M, dimer: D, and tetramer: T) after incubation with AS2 activator dATP (250 μM) and increasing concentrations of either GTP, Ac-TP, or Gc-TP between 0 and 1200 μM. Data shown are representative of three independent experiments. D , quantification of relative abundance of monomer, dimer, and tetramer oligomeric states as seen in C . Intensities are grouped by oligomeric state, and colors indicate different AS1 activators. Data points indicate means of three independent experiments; error bars indicate SD. mant-GTP, 2'/3′-O- N -methyl-anthraniloyl)-GTP; SAMHD1, SAM and HD domain–containing protein 1.

    Techniques Used: Competitive Binding Assay, Fluorescence, Incubation, Binding Assay

    SAMHD1 is an allosterically activated dNTP hydrolase . A , schematic representation of the current model of SAMHD1 allosteric activation and oligomerization. Inactive SAMHD1 monomers dimerize upon binding of (d)GTP to allosteric site 1 (AS1). Upon binding of any dNTP to allosteric site 2 (AS2), the catalytically active homotetramer is formed. B , the guanine nucleotide analogs acyclovir-triphosphate (Ac-TP) and ganciclovir-triphosphate (Gc-TP) closely resemble SAMHD1 AS1 activator GTP. SAMHD1, SAM and HD domain–containing protein 1.
    Figure Legend Snippet: SAMHD1 is an allosterically activated dNTP hydrolase . A , schematic representation of the current model of SAMHD1 allosteric activation and oligomerization. Inactive SAMHD1 monomers dimerize upon binding of (d)GTP to allosteric site 1 (AS1). Upon binding of any dNTP to allosteric site 2 (AS2), the catalytically active homotetramer is formed. B , the guanine nucleotide analogs acyclovir-triphosphate (Ac-TP) and ganciclovir-triphosphate (Gc-TP) closely resemble SAMHD1 AS1 activator GTP. SAMHD1, SAM and HD domain–containing protein 1.

    Techniques Used: Activation Assay, Binding Assay

    Acyclovir-triphosphate (Ac-TP) and ganciclovir-triphosphate (Gc-TP) modulate SAMHD1 activity by changing the kinetic profile . A , an overlay of five NMR spectra, showing peaks for SAMHD1 substrate and activator dATP, as well as reaction product dA. Different measurement timepoints (2, 5, 10, 15, and 20 min after reaction start) show reaction progress over time. B , Michaelis–Menten (GTP) or allosteric sigmoidal (Ac-TP/Gc-TP) equation parameters fitted to experimental data by least squares regression for the depletion of 500 μM dATP in the presence of 250 μM GTP, Ac-TP, or Gc-TP AS1 activator by SAMHD1 (1 μM). Data are shown representative of three independent experiments. NMR spectra were recorded in 30 s intervals for GTP- and Ac-TP-activated SAMHD1 and 5- or 7-min intervals for Gc-TP-activated SAMHD1. Estimated Michaelis–Menten equation parameters for GTP-activated dATP depletion (numbers in brackets indicate SD for three experimental replicates): k cat : 0.88 s -1 (±0.54 s -1 ), K M : 140 μM (±84 μM), k cat / K M : 0.006 μM -1 s -1 (±0.001 μM -1 s -1 ). Estimated allosteric sigmoidal equation parameters for Ac-TP-activated dATP depletion (numbers in brackets indicate SD for three experimental replicates): k cat : 0.99 s -1 (±0.58 s -1 ), K half : 244 μM (±46 μM), h: 2.1 (±0.2), k cat / K half : 0.004 μM -1 s -1 (±0.002 μM -1 s -1 ). Estimated allosteric sigmoidal equation parameters for Gc-TP-activated dATP depletion (numbers in brackets indicate SD for three replicates): k cat : 0.03 s -1 (±0.01 s -1 ), K half : 211 μM (±25 μM), h: 3.1 (±0.6), k cat / K half : 0.13 nM -1 s -1 (±0.08 nM -1 s -1 ). SAMHD1, SAM and HD domain–containing protein 1.
    Figure Legend Snippet: Acyclovir-triphosphate (Ac-TP) and ganciclovir-triphosphate (Gc-TP) modulate SAMHD1 activity by changing the kinetic profile . A , an overlay of five NMR spectra, showing peaks for SAMHD1 substrate and activator dATP, as well as reaction product dA. Different measurement timepoints (2, 5, 10, 15, and 20 min after reaction start) show reaction progress over time. B , Michaelis–Menten (GTP) or allosteric sigmoidal (Ac-TP/Gc-TP) equation parameters fitted to experimental data by least squares regression for the depletion of 500 μM dATP in the presence of 250 μM GTP, Ac-TP, or Gc-TP AS1 activator by SAMHD1 (1 μM). Data are shown representative of three independent experiments. NMR spectra were recorded in 30 s intervals for GTP- and Ac-TP-activated SAMHD1 and 5- or 7-min intervals for Gc-TP-activated SAMHD1. Estimated Michaelis–Menten equation parameters for GTP-activated dATP depletion (numbers in brackets indicate SD for three experimental replicates): k cat : 0.88 s -1 (±0.54 s -1 ), K M : 140 μM (±84 μM), k cat / K M : 0.006 μM -1 s -1 (±0.001 μM -1 s -1 ). Estimated allosteric sigmoidal equation parameters for Ac-TP-activated dATP depletion (numbers in brackets indicate SD for three experimental replicates): k cat : 0.99 s -1 (±0.58 s -1 ), K half : 244 μM (±46 μM), h: 2.1 (±0.2), k cat / K half : 0.004 μM -1 s -1 (±0.002 μM -1 s -1 ). Estimated allosteric sigmoidal equation parameters for Gc-TP-activated dATP depletion (numbers in brackets indicate SD for three replicates): k cat : 0.03 s -1 (±0.01 s -1 ), K half : 211 μM (±25 μM), h: 3.1 (±0.6), k cat / K half : 0.13 nM -1 s -1 (±0.08 nM -1 s -1 ). SAMHD1, SAM and HD domain–containing protein 1.

    Techniques Used: Activity Assay

    Combination of GTP and acyclovir-triphosphate (Ac-TP)/ganciclovir-triphosphate (Gc-TP) allosteric activators promotes SAMHD1 activity . A , a schematic representation of the experiment flow. SAMHD1 was preincubated with varying concentrations of GTP (0–50 μM, indicated by color gradient in B – D ), followed by the simultaneous addition of varying concentrations of AS1-activators GTP ( B ), Ac-TP ( C ), or Gc-TP ( D ) (0–50 μM) and a fixed concentration of AS2-activator and substrate dATP (50 μM). B – D , dATP substrate turnover was quantified using the enzyme-coupled activity assay, and activity was normalized to GTP (50 μM, preincubation) + GTP (50 μM, added) control. Select experimental conditions are highlighted as bar charts for easier comparison. Left , data points indicate means of three independent experiments; each performed with technical duplicates; error bars indicate SD. Right , bars indicate means of three independent experiments, where dots represent individual values of technical duplicates. Error bars indicate SD. SAMHD1, SAM and HD domain–containing protein 1.
    Figure Legend Snippet: Combination of GTP and acyclovir-triphosphate (Ac-TP)/ganciclovir-triphosphate (Gc-TP) allosteric activators promotes SAMHD1 activity . A , a schematic representation of the experiment flow. SAMHD1 was preincubated with varying concentrations of GTP (0–50 μM, indicated by color gradient in B – D ), followed by the simultaneous addition of varying concentrations of AS1-activators GTP ( B ), Ac-TP ( C ), or Gc-TP ( D ) (0–50 μM) and a fixed concentration of AS2-activator and substrate dATP (50 μM). B – D , dATP substrate turnover was quantified using the enzyme-coupled activity assay, and activity was normalized to GTP (50 μM, preincubation) + GTP (50 μM, added) control. Select experimental conditions are highlighted as bar charts for easier comparison. Left , data points indicate means of three independent experiments; each performed with technical duplicates; error bars indicate SD. Right , bars indicate means of three independent experiments, where dots represent individual values of technical duplicates. Error bars indicate SD. SAMHD1, SAM and HD domain–containing protein 1.

    Techniques Used: Activity Assay, Concentration Assay, Control, Comparison

    Antiviral nucleotide analogs fine-tune SAMHD1 dNTPase activity . A , in the presence of guanine nucleotide analogs, Ac-TP and Gc-TP, SAMHD1 forms homotetramers that are catalytically competent but display reduced catalytic activity with distinct kinetic profiles compared with those containing the endogenous activator GTP. B , due to the cooperativity between Ac-TP/Gc-TP and GTP in allosterically activating SAMHD1, we suggest the existence of mixed SAMHD1 tetramers where a mixture of GTP- and analog-bound monomers make up a homotetramer. The resulting mixed tetramers can display enzymatic activity comparable with GTP-only-activated SAMHD1. Ac-TP, acyclovir-triphosphate; Gc-TP, ganciclovir-triphosphate; SAMHD1, SAM and HD domain–containing protein 1.
    Figure Legend Snippet: Antiviral nucleotide analogs fine-tune SAMHD1 dNTPase activity . A , in the presence of guanine nucleotide analogs, Ac-TP and Gc-TP, SAMHD1 forms homotetramers that are catalytically competent but display reduced catalytic activity with distinct kinetic profiles compared with those containing the endogenous activator GTP. B , due to the cooperativity between Ac-TP/Gc-TP and GTP in allosterically activating SAMHD1, we suggest the existence of mixed SAMHD1 tetramers where a mixture of GTP- and analog-bound monomers make up a homotetramer. The resulting mixed tetramers can display enzymatic activity comparable with GTP-only-activated SAMHD1. Ac-TP, acyclovir-triphosphate; Gc-TP, ganciclovir-triphosphate; SAMHD1, SAM and HD domain–containing protein 1.

    Techniques Used: Activity Assay

    Related Articles

    Enzymatic Assay:

    Article Title: Allosteric targeting with antiviral nucleotide analogs allows fine-tuning of SAMHD1 dNTPase activity
    Article Snippet: Ac-TP (NU-877), Gc-TP (NU-275), dGTPαS (NU-424), mant-GTP (NU-206), and ara-CTP (NU-117) were obtained from Jena Bioscience. dATP (27-1850-04), dCTP (27-1850-04), and dTTP (27-1880-04) were obtained from GE Healthcare.

    Incubation:

    Article Title: Allosteric targeting with antiviral nucleotide analogs allows fine-tuning of SAMHD1 dNTPase activity
    Article Snippet: Ac-TP (NU-877), Gc-TP (NU-275), dGTPαS (NU-424), mant-GTP (NU-206), and ara-CTP (NU-117) were obtained from Jena Bioscience. dATP (27-1850-04), dCTP (27-1850-04), and dTTP (27-1880-04) were obtained from GE Healthcare.

    Control:

    Article Title: Allosteric targeting with antiviral nucleotide analogs allows fine-tuning of SAMHD1 dNTPase activity
    Article Snippet: Ac-TP (NU-877), Gc-TP (NU-275), dGTPαS (NU-424), mant-GTP (NU-206), and ara-CTP (NU-117) were obtained from Jena Bioscience. dATP (27-1850-04), dCTP (27-1850-04), and dTTP (27-1880-04) were obtained from GE Healthcare.

    Activity Assay:

    Article Title: Allosteric targeting with antiviral nucleotide analogs allows fine-tuning of SAMHD1 dNTPase activity
    Article Snippet: Ac-TP (NU-877), Gc-TP (NU-275), dGTPαS (NU-424), mant-GTP (NU-206), and ara-CTP (NU-117) were obtained from Jena Bioscience. dATP (27-1850-04), dCTP (27-1850-04), and dTTP (27-1880-04) were obtained from GE Healthcare.

    Competitive Binding Assay:

    Article Title: Allosteric targeting with antiviral nucleotide analogs allows fine-tuning of SAMHD1 dNTPase activity
    Article Snippet: Ac-TP (NU-877), Gc-TP (NU-275), dGTPαS (NU-424), mant-GTP (NU-206), and ara-CTP (NU-117) were obtained from Jena Bioscience. dATP (27-1850-04), dCTP (27-1850-04), and dTTP (27-1880-04) were obtained from GE Healthcare.

    Fluorescence:

    Article Title: Allosteric targeting with antiviral nucleotide analogs allows fine-tuning of SAMHD1 dNTPase activity
    Article Snippet: Ac-TP (NU-877), Gc-TP (NU-275), dGTPαS (NU-424), mant-GTP (NU-206), and ara-CTP (NU-117) were obtained from Jena Bioscience. dATP (27-1850-04), dCTP (27-1850-04), and dTTP (27-1880-04) were obtained from GE Healthcare.

    Binding Assay:

    Article Title: Allosteric targeting with antiviral nucleotide analogs allows fine-tuning of SAMHD1 dNTPase activity
    Article Snippet: Ac-TP (NU-877), Gc-TP (NU-275), dGTPαS (NU-424), mant-GTP (NU-206), and ara-CTP (NU-117) were obtained from Jena Bioscience. dATP (27-1850-04), dCTP (27-1850-04), and dTTP (27-1880-04) were obtained from GE Healthcare.

    Activation Assay:

    Article Title: Allosteric targeting with antiviral nucleotide analogs allows fine-tuning of SAMHD1 dNTPase activity
    Article Snippet: Ac-TP (NU-877), Gc-TP (NU-275), dGTPαS (NU-424), mant-GTP (NU-206), and ara-CTP (NU-117) were obtained from Jena Bioscience. dATP (27-1850-04), dCTP (27-1850-04), and dTTP (27-1880-04) were obtained from GE Healthcare.

    Concentration Assay:

    Article Title: Allosteric targeting with antiviral nucleotide analogs allows fine-tuning of SAMHD1 dNTPase activity
    Article Snippet: Ac-TP (NU-877), Gc-TP (NU-275), dGTPαS (NU-424), mant-GTP (NU-206), and ara-CTP (NU-117) were obtained from Jena Bioscience. dATP (27-1850-04), dCTP (27-1850-04), and dTTP (27-1880-04) were obtained from GE Healthcare.

    Comparison:

    Article Title: Allosteric targeting with antiviral nucleotide analogs allows fine-tuning of SAMHD1 dNTPase activity
    Article Snippet: Ac-TP (NU-877), Gc-TP (NU-275), dGTPαS (NU-424), mant-GTP (NU-206), and ara-CTP (NU-117) were obtained from Jena Bioscience. dATP (27-1850-04), dCTP (27-1850-04), and dTTP (27-1880-04) were obtained from GE Healthcare.



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    Image Search Results


    Acyclovir-triphosphate (Ac-TP) and ganciclovir-triphosphate (Gc-TP) are allosteric site 1 (AS1) activators that differentially activate dNTP hydrolysis . A , rationale of the enzymatic assay. SAMHD1 is incubated with test compounds (100 μM,

    Journal: The Journal of Biological Chemistry

    Article Title: Allosteric targeting with antiviral nucleotide analogs allows fine-tuning of SAMHD1 dNTPase activity

    doi: 10.1016/j.jbc.2026.111214

    Figure Lengend Snippet: Acyclovir-triphosphate (Ac-TP) and ganciclovir-triphosphate (Gc-TP) are allosteric site 1 (AS1) activators that differentially activate dNTP hydrolysis . A , rationale of the enzymatic assay. SAMHD1 is incubated with test compounds (100 μM, "X") and allosteric activators, substrates, or buffer (indicated by color ), allowing determination of where test compounds bind. Control compounds: GTP (AS1-activator), dGTP (AS1-/AS2-activator/substrate), and dATP (AS2-activator/substrate). B , SAMHD1 was incubated with different combinations of activators/substrates/buffer (indicated by color ) and test compounds ( left ) in the enzyme-coupled assay. SAMHD1 activity normalized to buffer + dGTP (100 μM) control. Bars indicate means of three independent experiments, where dots represent individual values of technical duplicates. Error bars indicate SD. C , SAMHD1 was incubated with varying concentrations of GTP, Ac-TP, or Gc-TP and 100 μM of the indicated dNTP in the enzyme-coupled assay. SAMHD1 activity was normalized to dATP (100 μM) + GTP (100 μM) control. Data points indicate the mean of two independent experiments; each performed with technical duplicates; error bars indicate SD. SAMHD1, SAM and HD domain–containing protein 1.

    Article Snippet: Ac-TP (NU-877), Gc-TP (NU-275), dGTPαS (NU-424), mant-GTP (NU-206), and ara-CTP (NU-117) were obtained from Jena Bioscience. dATP (27-1850-04), dCTP (27-1850-04), and dTTP (27-1880-04) were obtained from GE Healthcare.

    Techniques: Enzymatic Assay, Incubation, Control, Activity Assay

    Acyclovir-triphosphate (Ac-TP) and ganciclovir-triphosphate (Gc-TP) bind to allosteric site 1 (AS1) and induce tetramerization . A , schematic of the AS1 competitive binding assay using the environmentally sensitive mant-GTP probe. As mant-GTP is displaced from AS1 by competitors, fluorescence signal decreases. B , SAMHD1 (2 μM) and mant-GTP (0.5 μM) were incubated with varying concentrations of AS1 competitors. Data points indicate means of three independent experiments; each performed with technical duplicates. No-compound controls for each competitor dilution series were considered as shared technical replicates (N = 6). Error bars indicate SD. p K i values ± SD were calculated from a competitive binding equation (see the section). ANOVA shows significant differences between p K i values for the three AS1 competitors ( p = 0.0007). Results of a post hoc Tukey’s multiple comparisons are indicated by asterisks , where ∗∗∗ and ∗∗ indicate adjusted p values ≤0.001 and ≤0.01, respectively. GTP versus Ac-TP: adjusted p = 0.0006; GTP versus Gc-TP: adjusted p = 0.0041; and Ac-TP versus Gc-TP: adjusted p = 0.1331. C , mass photometry quantification of SAMHD1 oligomeric states (monomer: M, dimer: D, and tetramer: T) after incubation with AS2 activator dATP (250 μM) and increasing concentrations of either GTP, Ac-TP, or Gc-TP between 0 and 1200 μM. Data shown are representative of three independent experiments. D , quantification of relative abundance of monomer, dimer, and tetramer oligomeric states as seen in C . Intensities are grouped by oligomeric state, and colors indicate different AS1 activators. Data points indicate means of three independent experiments; error bars indicate SD. mant-GTP, 2'/3′-O- N -methyl-anthraniloyl)-GTP; SAMHD1, SAM and HD domain–containing protein 1.

    Journal: The Journal of Biological Chemistry

    Article Title: Allosteric targeting with antiviral nucleotide analogs allows fine-tuning of SAMHD1 dNTPase activity

    doi: 10.1016/j.jbc.2026.111214

    Figure Lengend Snippet: Acyclovir-triphosphate (Ac-TP) and ganciclovir-triphosphate (Gc-TP) bind to allosteric site 1 (AS1) and induce tetramerization . A , schematic of the AS1 competitive binding assay using the environmentally sensitive mant-GTP probe. As mant-GTP is displaced from AS1 by competitors, fluorescence signal decreases. B , SAMHD1 (2 μM) and mant-GTP (0.5 μM) were incubated with varying concentrations of AS1 competitors. Data points indicate means of three independent experiments; each performed with technical duplicates. No-compound controls for each competitor dilution series were considered as shared technical replicates (N = 6). Error bars indicate SD. p K i values ± SD were calculated from a competitive binding equation (see the section). ANOVA shows significant differences between p K i values for the three AS1 competitors ( p = 0.0007). Results of a post hoc Tukey’s multiple comparisons are indicated by asterisks , where ∗∗∗ and ∗∗ indicate adjusted p values ≤0.001 and ≤0.01, respectively. GTP versus Ac-TP: adjusted p = 0.0006; GTP versus Gc-TP: adjusted p = 0.0041; and Ac-TP versus Gc-TP: adjusted p = 0.1331. C , mass photometry quantification of SAMHD1 oligomeric states (monomer: M, dimer: D, and tetramer: T) after incubation with AS2 activator dATP (250 μM) and increasing concentrations of either GTP, Ac-TP, or Gc-TP between 0 and 1200 μM. Data shown are representative of three independent experiments. D , quantification of relative abundance of monomer, dimer, and tetramer oligomeric states as seen in C . Intensities are grouped by oligomeric state, and colors indicate different AS1 activators. Data points indicate means of three independent experiments; error bars indicate SD. mant-GTP, 2'/3′-O- N -methyl-anthraniloyl)-GTP; SAMHD1, SAM and HD domain–containing protein 1.

    Article Snippet: Ac-TP (NU-877), Gc-TP (NU-275), dGTPαS (NU-424), mant-GTP (NU-206), and ara-CTP (NU-117) were obtained from Jena Bioscience. dATP (27-1850-04), dCTP (27-1850-04), and dTTP (27-1880-04) were obtained from GE Healthcare.

    Techniques: Competitive Binding Assay, Fluorescence, Incubation, Binding Assay

    SAMHD1 is an allosterically activated dNTP hydrolase . A , schematic representation of the current model of SAMHD1 allosteric activation and oligomerization. Inactive SAMHD1 monomers dimerize upon binding of (d)GTP to allosteric site 1 (AS1). Upon binding of any dNTP to allosteric site 2 (AS2), the catalytically active homotetramer is formed. B , the guanine nucleotide analogs acyclovir-triphosphate (Ac-TP) and ganciclovir-triphosphate (Gc-TP) closely resemble SAMHD1 AS1 activator GTP. SAMHD1, SAM and HD domain–containing protein 1.

    Journal: The Journal of Biological Chemistry

    Article Title: Allosteric targeting with antiviral nucleotide analogs allows fine-tuning of SAMHD1 dNTPase activity

    doi: 10.1016/j.jbc.2026.111214

    Figure Lengend Snippet: SAMHD1 is an allosterically activated dNTP hydrolase . A , schematic representation of the current model of SAMHD1 allosteric activation and oligomerization. Inactive SAMHD1 monomers dimerize upon binding of (d)GTP to allosteric site 1 (AS1). Upon binding of any dNTP to allosteric site 2 (AS2), the catalytically active homotetramer is formed. B , the guanine nucleotide analogs acyclovir-triphosphate (Ac-TP) and ganciclovir-triphosphate (Gc-TP) closely resemble SAMHD1 AS1 activator GTP. SAMHD1, SAM and HD domain–containing protein 1.

    Article Snippet: Ac-TP (NU-877), Gc-TP (NU-275), dGTPαS (NU-424), mant-GTP (NU-206), and ara-CTP (NU-117) were obtained from Jena Bioscience. dATP (27-1850-04), dCTP (27-1850-04), and dTTP (27-1880-04) were obtained from GE Healthcare.

    Techniques: Activation Assay, Binding Assay

    Acyclovir-triphosphate (Ac-TP) and ganciclovir-triphosphate (Gc-TP) modulate SAMHD1 activity by changing the kinetic profile . A , an overlay of five NMR spectra, showing peaks for SAMHD1 substrate and activator dATP, as well as reaction product dA. Different measurement timepoints (2, 5, 10, 15, and 20 min after reaction start) show reaction progress over time. B , Michaelis–Menten (GTP) or allosteric sigmoidal (Ac-TP/Gc-TP) equation parameters fitted to experimental data by least squares regression for the depletion of 500 μM dATP in the presence of 250 μM GTP, Ac-TP, or Gc-TP AS1 activator by SAMHD1 (1 μM). Data are shown representative of three independent experiments. NMR spectra were recorded in 30 s intervals for GTP- and Ac-TP-activated SAMHD1 and 5- or 7-min intervals for Gc-TP-activated SAMHD1. Estimated Michaelis–Menten equation parameters for GTP-activated dATP depletion (numbers in brackets indicate SD for three experimental replicates): k cat : 0.88 s -1 (±0.54 s -1 ), K M : 140 μM (±84 μM), k cat / K M : 0.006 μM -1 s -1 (±0.001 μM -1 s -1 ). Estimated allosteric sigmoidal equation parameters for Ac-TP-activated dATP depletion (numbers in brackets indicate SD for three experimental replicates): k cat : 0.99 s -1 (±0.58 s -1 ), K half : 244 μM (±46 μM), h: 2.1 (±0.2), k cat / K half : 0.004 μM -1 s -1 (±0.002 μM -1 s -1 ). Estimated allosteric sigmoidal equation parameters for Gc-TP-activated dATP depletion (numbers in brackets indicate SD for three replicates): k cat : 0.03 s -1 (±0.01 s -1 ), K half : 211 μM (±25 μM), h: 3.1 (±0.6), k cat / K half : 0.13 nM -1 s -1 (±0.08 nM -1 s -1 ). SAMHD1, SAM and HD domain–containing protein 1.

    Journal: The Journal of Biological Chemistry

    Article Title: Allosteric targeting with antiviral nucleotide analogs allows fine-tuning of SAMHD1 dNTPase activity

    doi: 10.1016/j.jbc.2026.111214

    Figure Lengend Snippet: Acyclovir-triphosphate (Ac-TP) and ganciclovir-triphosphate (Gc-TP) modulate SAMHD1 activity by changing the kinetic profile . A , an overlay of five NMR spectra, showing peaks for SAMHD1 substrate and activator dATP, as well as reaction product dA. Different measurement timepoints (2, 5, 10, 15, and 20 min after reaction start) show reaction progress over time. B , Michaelis–Menten (GTP) or allosteric sigmoidal (Ac-TP/Gc-TP) equation parameters fitted to experimental data by least squares regression for the depletion of 500 μM dATP in the presence of 250 μM GTP, Ac-TP, or Gc-TP AS1 activator by SAMHD1 (1 μM). Data are shown representative of three independent experiments. NMR spectra were recorded in 30 s intervals for GTP- and Ac-TP-activated SAMHD1 and 5- or 7-min intervals for Gc-TP-activated SAMHD1. Estimated Michaelis–Menten equation parameters for GTP-activated dATP depletion (numbers in brackets indicate SD for three experimental replicates): k cat : 0.88 s -1 (±0.54 s -1 ), K M : 140 μM (±84 μM), k cat / K M : 0.006 μM -1 s -1 (±0.001 μM -1 s -1 ). Estimated allosteric sigmoidal equation parameters for Ac-TP-activated dATP depletion (numbers in brackets indicate SD for three experimental replicates): k cat : 0.99 s -1 (±0.58 s -1 ), K half : 244 μM (±46 μM), h: 2.1 (±0.2), k cat / K half : 0.004 μM -1 s -1 (±0.002 μM -1 s -1 ). Estimated allosteric sigmoidal equation parameters for Gc-TP-activated dATP depletion (numbers in brackets indicate SD for three replicates): k cat : 0.03 s -1 (±0.01 s -1 ), K half : 211 μM (±25 μM), h: 3.1 (±0.6), k cat / K half : 0.13 nM -1 s -1 (±0.08 nM -1 s -1 ). SAMHD1, SAM and HD domain–containing protein 1.

    Article Snippet: Ac-TP (NU-877), Gc-TP (NU-275), dGTPαS (NU-424), mant-GTP (NU-206), and ara-CTP (NU-117) were obtained from Jena Bioscience. dATP (27-1850-04), dCTP (27-1850-04), and dTTP (27-1880-04) were obtained from GE Healthcare.

    Techniques: Activity Assay

    Combination of GTP and acyclovir-triphosphate (Ac-TP)/ganciclovir-triphosphate (Gc-TP) allosteric activators promotes SAMHD1 activity . A , a schematic representation of the experiment flow. SAMHD1 was preincubated with varying concentrations of GTP (0–50 μM, indicated by color gradient in B – D ), followed by the simultaneous addition of varying concentrations of AS1-activators GTP ( B ), Ac-TP ( C ), or Gc-TP ( D ) (0–50 μM) and a fixed concentration of AS2-activator and substrate dATP (50 μM). B – D , dATP substrate turnover was quantified using the enzyme-coupled activity assay, and activity was normalized to GTP (50 μM, preincubation) + GTP (50 μM, added) control. Select experimental conditions are highlighted as bar charts for easier comparison. Left , data points indicate means of three independent experiments; each performed with technical duplicates; error bars indicate SD. Right , bars indicate means of three independent experiments, where dots represent individual values of technical duplicates. Error bars indicate SD. SAMHD1, SAM and HD domain–containing protein 1.

    Journal: The Journal of Biological Chemistry

    Article Title: Allosteric targeting with antiviral nucleotide analogs allows fine-tuning of SAMHD1 dNTPase activity

    doi: 10.1016/j.jbc.2026.111214

    Figure Lengend Snippet: Combination of GTP and acyclovir-triphosphate (Ac-TP)/ganciclovir-triphosphate (Gc-TP) allosteric activators promotes SAMHD1 activity . A , a schematic representation of the experiment flow. SAMHD1 was preincubated with varying concentrations of GTP (0–50 μM, indicated by color gradient in B – D ), followed by the simultaneous addition of varying concentrations of AS1-activators GTP ( B ), Ac-TP ( C ), or Gc-TP ( D ) (0–50 μM) and a fixed concentration of AS2-activator and substrate dATP (50 μM). B – D , dATP substrate turnover was quantified using the enzyme-coupled activity assay, and activity was normalized to GTP (50 μM, preincubation) + GTP (50 μM, added) control. Select experimental conditions are highlighted as bar charts for easier comparison. Left , data points indicate means of three independent experiments; each performed with technical duplicates; error bars indicate SD. Right , bars indicate means of three independent experiments, where dots represent individual values of technical duplicates. Error bars indicate SD. SAMHD1, SAM and HD domain–containing protein 1.

    Article Snippet: Ac-TP (NU-877), Gc-TP (NU-275), dGTPαS (NU-424), mant-GTP (NU-206), and ara-CTP (NU-117) were obtained from Jena Bioscience. dATP (27-1850-04), dCTP (27-1850-04), and dTTP (27-1880-04) were obtained from GE Healthcare.

    Techniques: Activity Assay, Concentration Assay, Control, Comparison

    Antiviral nucleotide analogs fine-tune SAMHD1 dNTPase activity . A , in the presence of guanine nucleotide analogs, Ac-TP and Gc-TP, SAMHD1 forms homotetramers that are catalytically competent but display reduced catalytic activity with distinct kinetic profiles compared with those containing the endogenous activator GTP. B , due to the cooperativity between Ac-TP/Gc-TP and GTP in allosterically activating SAMHD1, we suggest the existence of mixed SAMHD1 tetramers where a mixture of GTP- and analog-bound monomers make up a homotetramer. The resulting mixed tetramers can display enzymatic activity comparable with GTP-only-activated SAMHD1. Ac-TP, acyclovir-triphosphate; Gc-TP, ganciclovir-triphosphate; SAMHD1, SAM and HD domain–containing protein 1.

    Journal: The Journal of Biological Chemistry

    Article Title: Allosteric targeting with antiviral nucleotide analogs allows fine-tuning of SAMHD1 dNTPase activity

    doi: 10.1016/j.jbc.2026.111214

    Figure Lengend Snippet: Antiviral nucleotide analogs fine-tune SAMHD1 dNTPase activity . A , in the presence of guanine nucleotide analogs, Ac-TP and Gc-TP, SAMHD1 forms homotetramers that are catalytically competent but display reduced catalytic activity with distinct kinetic profiles compared with those containing the endogenous activator GTP. B , due to the cooperativity between Ac-TP/Gc-TP and GTP in allosterically activating SAMHD1, we suggest the existence of mixed SAMHD1 tetramers where a mixture of GTP- and analog-bound monomers make up a homotetramer. The resulting mixed tetramers can display enzymatic activity comparable with GTP-only-activated SAMHD1. Ac-TP, acyclovir-triphosphate; Gc-TP, ganciclovir-triphosphate; SAMHD1, SAM and HD domain–containing protein 1.

    Article Snippet: Ac-TP (NU-877), Gc-TP (NU-275), dGTPαS (NU-424), mant-GTP (NU-206), and ara-CTP (NU-117) were obtained from Jena Bioscience. dATP (27-1850-04), dCTP (27-1850-04), and dTTP (27-1880-04) were obtained from GE Healthcare.

    Techniques: Activity Assay