Enzymes
| UniProtKB help_outline | 437 proteins |
Reaction participants Show >> << Hide
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Namehelp_outline
N-acetylglycyl-tRNAGly
Identifier
RHEA-COMP:19766
Reactive part
help_outline
- Name help_outline 3'-N-acetylglycyladenylyl residue Identifier CHEBI:232036 Charge -1 Formula C14H17N6O8P SMILEShelp_outline N1([C@@H]2O[C@H](COP(*)(=O)[O-])[C@H]([C@H]2O)OC(CNC(C)=O)=O)C=NC=3C1=NC=NC3N 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 6,485 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline N-acetylglycine Identifier CHEBI:61887 Charge -1 Formula C4H6NO3 InChIKeyhelp_outline OKJIRPAQVSHGFK-UHFFFAOYSA-M SMILEShelp_outline CC(=O)NCC([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 1 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
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Namehelp_outline
tRNAGly
Identifier
RHEA-COMP:9664
Reactive part
help_outline
- Name help_outline AMP 3'-end residue Identifier CHEBI:78442 Charge -1 Formula C10H12N5O6P SMILEShelp_outline Nc1ncnc2n(cnc12)[C@@H]1O[C@H](COP([O-])(-*)=O)[C@@H](O)[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 79 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 9,932 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:81979 | RHEA:81980 | RHEA:81981 | RHEA:81982 | |
|---|---|---|---|---|
| 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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A tRNA-Acetylating Toxin and Detoxifying Enzyme in Mycobacterium tuberculosis.
Tomasi F.G., Hall A.M.J., Schweber J.T.P., Dulberger C.L., McGowen K., Liu Q., Fortune S.M., Helaine S., Rubin E.J.
Toxin-antitoxin (TA) systems allow bacteria to adapt to changing environments without altering gene expression. Despite being overrepresented in Mycobacterium tuberculosis, their physiological roles remain elusive. We describe a TA system in M. tuberculosis which we named TacAT due to its homology ... >> More
Toxin-antitoxin (TA) systems allow bacteria to adapt to changing environments without altering gene expression. Despite being overrepresented in Mycobacterium tuberculosis, their physiological roles remain elusive. We describe a TA system in M. tuberculosis which we named TacAT due to its homology to previously discovered systems in Salmonella. The toxin, TacT, blocks growth by acetylating glycyl-tRNAs and inhibiting translation. Its effects are reversed by the enzyme peptidyl tRNA hydrolase (Pth), which also cleaves peptidyl tRNAs that are prematurely released from stalled ribosomes. Pth is essential in most bacteria and thereby has been proposed as a promising drug target for complex pathogens like M. tuberculosis. Transposon sequencing data suggest that the <i>tacAT</i> operon is nonessential for M. tuberculosis growth <i>in vitro</i>, and premature stop mutations in this TA system present in some clinical isolates suggest that it is also dispensable <i>in vivo</i>. We assessed whether TacT modulates <i>pth</i> essentiality in M. tuberculosis because drugs targeting Pth might prompt resistance if TacAT is disrupted. We show that <i>pth</i> essentiality is unaffected by the absence of <i>tacAT</i>. These results highlight a fundamental aspect of mycobacterial biology and indicate that Pth's essential role hinges on its peptidyl-tRNA hydrolase activity. Our work underscores Pth's potential as a viable target for new antibiotics. <b>IMPORTANCE</b> The global rise in antibiotic-resistant tuberculosis has prompted an urgent search for new drugs. Toxin-antitoxin (TA) systems allow bacteria to adapt rapidly to environmental changes, and Mycobacterium tuberculosis encodes more TA systems than any known pathogen. We have characterized a new TA system in M. tuberculosis: the toxin, TacT, acetylates charged tRNA to block protein synthesis. TacT's effects are reversed by the essential bacterial enzyme peptidyl tRNA hydrolase (Pth), which is currently being explored as an antibiotic target. Pth also cleaves peptidyl tRNAs that are prematurely released from stalled ribosomes. We assessed whether TacT modulates <i>pth</i> essentiality in M. tuberculosis because drugs targeting Pth might prompt resistance if TacT is disrupted. We show that <i>pth</i> essentiality is unaffected by the absence of this TA system, indicating that Pth's essential role hinges on its peptidyl-tRNA hydrolase activity. Our work underscores Pth's potential as a viable target for new antibiotics. << Less
Microbiol. Spectr. 10:e0058022-e0058022(2022) [PubMed] [EuropePMC]
This publication is cited by 1 other entry.