Reaction participants Show >> << Hide
- Name help_outline dTTP Identifier CHEBI:37568 (Beilstein: 4628471) help_outline Charge -4 Formula C10H13N2O14P3 InChIKeyhelp_outline NHVNXKFIZYSCEB-XLPZGREQSA-J SMILEShelp_outline Cc1cn([C@H]2C[C@H](O)[C@@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)O2)c(=O)[nH]c1=O 2D coordinates Mol file for the small molecule Search links Involved in 9 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H2O Identifier CHEBI:15377 (Beilstein: 3587155; CAS: 7732-18-5) help_outline Charge 0 Formula H2O InChIKeyhelp_outline XLYOFNOQVPJJNP-UHFFFAOYSA-N SMILEShelp_outline [H]O[H] 2D coordinates Mol file for the small molecule Search links Involved in 6,204 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H+ Identifier CHEBI:15378 Charge 1 Formula H InChIKeyhelp_outline GPRLSGONYQIRFK-UHFFFAOYSA-N SMILEShelp_outline [H+] 2D coordinates Mol file for the small molecule Search links Involved in 9,431 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline thymidine Identifier CHEBI:17748 (Beilstein: 89285; CAS: 50-89-5) help_outline Charge 0 Formula C10H14N2O5 InChIKeyhelp_outline IQFYYKKMVGJFEH-XLPZGREQSA-N SMILEShelp_outline Cc1cn([C@H]2C[C@H](O)[C@@H](CO)O2)c(=O)[nH]c1=O 2D coordinates Mol file for the small molecule Search links Involved in 11 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline triphosphate Identifier CHEBI:18036 (CAS: 14127-68-5) help_outline Charge -5 Formula O10P3 InChIKeyhelp_outline UNXRWKVEANCORM-UHFFFAOYSA-I SMILEShelp_outline [O-]P([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 18 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:80079 | RHEA:80080 | RHEA:80081 | RHEA:80082 | |
|---|---|---|---|---|
| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
| UniProtKB help_outline |
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Related reactions help_outline
More general form(s) of this reaction
Publications
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Impaired dNTPase activity of SAMHD1 by phosphomimetic mutation of Thr-592.
Tang C., Ji X., Wu L., Xiong Y.
SAMHD1 is a cellular protein that plays key roles in HIV-1 restriction and regulation of cellular dNTP levels. Mutations in SAMHD1 are also implicated in the pathogenesis of chronic lymphocytic leukemia and Aicardi-Goutières syndrome. The anti-HIV-1 activity of SAMHD1 is negatively modulated by ph ... >> More
SAMHD1 is a cellular protein that plays key roles in HIV-1 restriction and regulation of cellular dNTP levels. Mutations in SAMHD1 are also implicated in the pathogenesis of chronic lymphocytic leukemia and Aicardi-Goutières syndrome. The anti-HIV-1 activity of SAMHD1 is negatively modulated by phosphorylation at residue Thr-592. The mechanism underlying the effect of phosphorylation on anti-HIV-1 activity remains unclear. SAMHD1 forms tetramers that possess deoxyribonucleotide triphosphate triphosphohydrolase (dNTPase) activity, which is allosterically controlled by the combined action of GTP and all four dNTPs. Here we demonstrate that the phosphomimetic mutation T592E reduces the stability of the SAMHD1 tetramer and the dNTPase activity of the enzyme. To better understand the underlying mechanisms, we determined the crystal structures of SAMHD1 variants T592E and T592V. Although the neutral substitution T592V does not perturb the structure, the charged T592E induces large conformational changes, likely triggered by electrostatic repulsion from a distinct negatively charged environment surrounding Thr-592. The phosphomimetic mutation results in a significant decrease in the population of active SAMHD1 tetramers, and hence the dNTPase activity is substantially decreased. These results provide a mechanistic understanding of how SAMHD1 phosphorylation at residue Thr-592 may modulate its cellular and antiviral functions. << Less
J. Biol. Chem. 290:26352-26359(2015) [PubMed] [EuropePMC]
This publication is cited by 3 other entries.
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Aicardi-Goutieres syndrome gene and HIV-1 restriction factor SAMHD1 is a dGTP-regulated deoxynucleotide triphosphohydrolase.
Powell R.D., Holland P.J., Hollis T., Perrino F.W.
The SAMHD1 protein is an HIV-1 restriction factor that is targeted by the HIV-2 accessory protein Vpx in myeloid lineage cells. Mutations in the SAMHD1 gene cause Aicardi-Goutières syndrome, a genetic disease that mimics congenital viral infection. To determine the physiological function of the SA ... >> More
The SAMHD1 protein is an HIV-1 restriction factor that is targeted by the HIV-2 accessory protein Vpx in myeloid lineage cells. Mutations in the SAMHD1 gene cause Aicardi-Goutières syndrome, a genetic disease that mimics congenital viral infection. To determine the physiological function of the SAMHD1 protein, the SAMHD1 gene was cloned, recombinant protein was produced, and the catalytic activity of the purified enzyme was identified. We show that SAMHD1 contains a dGTP-regulated deoxynucleotide triphosphohydrolase. We propose that Vpx targets SAMHD1 for degradation in a viral strategy to control cellular deoxynucleotide levels for efficient replication. << Less
J. Biol. Chem. 286:43596-43600(2011) [PubMed] [EuropePMC]
This publication is cited by 3 other entries.