Enzymes
| UniProtKB help_outline | 2,997 proteins |
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Namehelp_outline
an N-(ADP-α-D-ribosyl)-thymidine in DNA
Identifier
RHEA-COMP:18051
Reactive part
help_outline
- Name help_outline N-(ADP-α-D-ribosyl)-dTMP residue Identifier CHEBI:191199 Charge -3 Formula C25H31N7O20P3 SMILEShelp_outline CC1=CN([C@H]2C[C@H](O-*)[C@@H](COP([O-])(-*)=O)O2)C(=O)N([C@H]2O[C@H](COP([O-])(=O)OP([O-])(=O)OC[C@H]3O[C@H]([C@H](O)[C@@H]3O)N3C=NC4=C3N=CN=C4N)[C@@H](O)[C@H]2O)C1=O 2D coordinates Mol file for the small molecule Search links Involved in 2 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H2O Identifier CHEBI:15377 (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 6,648 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
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Namehelp_outline
a thymidine in DNA
Identifier
RHEA-COMP:13556
Reactive part
help_outline
- Name help_outline dTMP residue Identifier CHEBI:137386 Charge -1 Formula C10H12N2O7P SMILEShelp_outline C1=C(C)C(NC(N1[C@@H]2O[C@H](COP(=O)([O-])*)[C@H](C2)O*)=O)=O 2D coordinates Mol file for the small molecule Search links Involved in 3 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline ADP-D-ribose Identifier CHEBI:57967 Charge -2 Formula C15H21N5O14P2 InChIKeyhelp_outline SRNWOUGRCWSEMX-TYASJMOZSA-L SMILEShelp_outline Nc1ncnc2n(cnc12)[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OC[C@H]2OC(O)[C@H](O)[C@@H]2O)[C@@H](O)[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 24 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:71655 | RHEA:71656 | RHEA:71657 | RHEA:71658 | |
|---|---|---|---|---|
| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
| UniProtKB help_outline |
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Publications
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The Toxin-Antitoxin System DarTG Catalyzes Reversible ADP-Ribosylation of DNA.
Jankevicius G., Ariza A., Ahel M., Ahel I.
The discovery and study of toxin-antitoxin (TA) systems helps us advance our understanding of the strategies prokaryotes employ to regulate cellular processes related to the general stress response, such as defense against phages, growth control, biofilm formation, persistence, and programmed cell ... >> More
The discovery and study of toxin-antitoxin (TA) systems helps us advance our understanding of the strategies prokaryotes employ to regulate cellular processes related to the general stress response, such as defense against phages, growth control, biofilm formation, persistence, and programmed cell death. Here we identify and characterize a TA system found in various bacteria, including the global pathogen Mycobacterium tuberculosis. The toxin of the system (DarT) is a domain of unknown function (DUF) 4433, and the antitoxin (DarG) a macrodomain protein. We demonstrate that DarT is an enzyme that specifically modifies thymidines on single-stranded DNA in a sequence-specific manner by a nucleotide-type modification called ADP-ribosylation. We also show that this modification can be removed by DarG. Our results provide an example of reversible DNA ADP-ribosylation, and we anticipate potential therapeutic benefits by targeting this enzyme-enzyme TA system in bacterial pathogens such as M. tuberculosis. << Less
Mol. Cell 64:1109-1116(2016) [PubMed] [EuropePMC]
This publication is cited by 1 other entry.
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DNA ADP-Ribosylation Stalls Replication and Is Reversed by RecF-Mediated Homologous Recombination and Nucleotide Excision Repair.
Lawaree E., Jankevicius G., Cooper C., Ahel I., Uphoff S., Tang C.M.
ADP-ribosylation of proteins is crucial for fundamental cellular processes. Despite increasing examples of DNA ADP-ribosylation, the impact of this modification on DNA metabolism and cell physiology is unknown. Here, we show that the DarTG toxin-antitoxin system from enteropathogenic Escherichia c ... >> More
ADP-ribosylation of proteins is crucial for fundamental cellular processes. Despite increasing examples of DNA ADP-ribosylation, the impact of this modification on DNA metabolism and cell physiology is unknown. Here, we show that the DarTG toxin-antitoxin system from enteropathogenic Escherichia coli (EPEC) catalyzes reversible ADP-ribosylation of single-stranded DNA (ssDNA). The DarT toxin recognizes specific sequence motifs. EPEC DarG abrogates DarT toxicity by two distinct mechanisms: removal of DNA ADP-ribose (ADPr) groups and DarT sequestration. Furthermore, we investigate how cells recognize and deal with DNA ADP-ribosylation. We demonstrate that DNA ADPr stalls replication and is perceived as DNA damage. Removal of ADPr from DNA requires the sequential activity of two DNA repair pathways, with RecF-mediated homologous recombination likely to transfer ADP-ribosylation from single-to double-stranded DNA (dsDNA) and subsequent nucleotide excision repair eliminating the lesion. Our work demonstrates that these DNA repair pathways prevent the genotoxic effects of DNA ADP-ribosylation. << Less
Cell Rep. 30:1373-1384(2020) [PubMed] [EuropePMC]
This publication is cited by 1 other entry.