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acetyltransferase toxins, TacTs - Coggle Diagram

- - - - Class II TA operons encode a non-secreted toxin, which inhibits an essential cellular function such as RNA translation or DNA replication, and an antitoxin that interacts with and neutralizes the toxin.
      - The toxin is relatively stable, whereas the antitoxin is labile and degraded under various stress conditions, leading to the build-up of free toxin and growth arrest of the bacterial cell.
      - Toxin, TacT, contributes to Salmonella Typhimurium entry into the persister state through acetylation of aminoacyl-tRNA molecules, thereby halting translation.
- - - - Overexpression of the TacT2STm had no noticeable effect on S. Typhimurium growth, whereas overexpression of TacT2SEn extended the lag phase dramatically.
      - Overexpression of the TacT3 dramatically extended the lag phase of S. Typhimurium
      - This growth inhibition was counteracted by concomitant overexpression of the corresponding antitoxin TacA2 or TacA3 gene.
      - :check:TacAT2SEn and TacAT3 operons encode functional TA modules.
- - - - TacT acetylates the primary amine group of the amino acid on charged tRNA molecules, thereby blocking peptide bond formation and protein synthesis.
        we considered that TacT2STm was a functional acetyltransferase.
      - All toxins inhibited production of DHFR when supplemented with Ac-CoA, although to different extents
  - - - TacT3 appeared to be the most potent toxin, and comparison of its active site with that of TacT revealed a difference in the orientation of Ac-CoA.
      - The adenine moiety is bent and more engaged in the binding pocket of TacT compared to that of TacT3, most likely owing to the bulky side chain of the Trp142 residue present in TacT3.
      - In TacT3, the adenine base of Ac-CoA is further stabilized outside the binding pocket by a hydrogen bond between its amine group and a carbonyl oxygen of the Gly145 residue.
      - Different conformation allows rapid unloading of coenzyme A after transfer of the acetyl moiety to the target substrate, increasing the processivity of the enzyme.
  - - - :check:Altogether, these results show that all TacT-like toxins present in Salmonella Typhimurium and Enteritidis block the primary amine group of the amino acid on charged tRNA molecules, and that they do this to different extent.
- - - - :check:K31E substitution abolished toxicity of TacT in Salmonella