Enzymes
UniProtKB help_outline | 6 proteins |
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- Name help_outline dATP Identifier CHEBI:61404 Charge -4 Formula C10H12N5O12P3 InChIKeyhelp_outline SUYVUBYJARFZHO-RRKCRQDMSA-J SMILEShelp_outline Nc1ncnc2n(cnc12)[C@H]1C[C@H](O)[C@@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)O1 2D coordinates Mol file for the small molecule Search links Involved in 14 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 2'-deoxyadenosine Identifier CHEBI:17256 (Beilstein: 91015; CAS: 958-09-8) help_outline Charge 0 Formula C10H13N5O3 InChIKeyhelp_outline OLXZPDWKRNYJJZ-RRKCRQDMSA-N SMILEShelp_outline Nc1ncnc2n(cnc12)[C@H]1C[C@H](O)[C@@H](CO)O1 2D coordinates Mol file for the small molecule Search links Involved in 8 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 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:67648 | RHEA:67649 | RHEA:67650 | RHEA:67651 | |
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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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A widespread pathway for substitution of adenine by diaminopurine in phage genomes.
Zhou Y., Xu X., Wei Y., Cheng Y., Guo Y., Khudyakov I., Liu F., He P., Song Z., Li Z., Gao Y., Ang E.L., Zhao H., Zhang Y., Zhao S.
DNA modifications vary in form and function but generally do not alter Watson-Crick base pairing. Diaminopurine (Z) is an exception because it completely replaces adenine and forms three hydrogen bonds with thymine in cyanophage S-2L genomic DNA. However, the biosynthesis, prevalence, and importan ... >> More
DNA modifications vary in form and function but generally do not alter Watson-Crick base pairing. Diaminopurine (Z) is an exception because it completely replaces adenine and forms three hydrogen bonds with thymine in cyanophage S-2L genomic DNA. However, the biosynthesis, prevalence, and importance of Z genomes remain unexplored. Here, we report a multienzyme system that supports Z-genome synthesis. We identified dozens of globally widespread phages harboring such enzymes, and we further verified the Z genome in one of these phages, <i>Acinetobacter</i> phage SH-Ab 15497, by using liquid chromatography with ultraviolet and mass spectrometry. The Z genome endows phages with evolutionary advantages for evading the attack of host restriction enzymes, and the characterization of its biosynthetic pathway enables Z-DNA production on a large scale for a diverse range of applications. << Less
Science 372:512-516(2021) [PubMed] [EuropePMC]
This publication is cited by 8 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.