ParST is a widespread toxin-antitoxin module that targets nucleotide metabolism.

TitleParST is a widespread toxin-antitoxin module that targets nucleotide metabolism.
Publication TypeJournal Article
Year of Publication2019
AuthorsPiscotta, FJ, Jeffrey, PD, A Link, J
JournalProc Natl Acad Sci U S A
Date Published2019 Jan 15
KeywordsADP Ribose Transferases, Amino Acid Sequence, Crystallography, Escherichia coli, Nucleotides, Ribose-Phosphate Pyrophosphokinase, Sphingomonadaceae, Toxin-Antitoxin Systems

<p>Toxin-antitoxin (TA) systems interfere with essential cellular processes and are implicated in bacterial lifestyle adaptations such as persistence and the biofilm formation. Here, we present structural, biochemical, and functional data on an uncharacterized TA system, the COG5654-COG5642 pair. Bioinformatic analysis showed that this TA pair is found in 2,942 of the 16,286 distinct bacterial species in the RefSeq database. We solved a structure of the toxin bound to a fragment of the antitoxin to 1.50 Å. This structure suggested that the toxin is a mono-ADP-ribosyltransferase (mART). The toxin specifically modifies phosphoribosyl pyrophosphate synthetase (Prs), an essential enzyme in nucleotide biosynthesis conserved in all organisms. We propose renaming the toxin ParT for Prs ADP-ribosylating toxin and ParS for the cognate antitoxin. ParT is a unique example of an intracellular protein mART in bacteria and is the smallest known mART. This work demonstrates that TA systems can induce bacteriostasis through interference with nucleotide biosynthesis.</p>

Alternate JournalProc Natl Acad Sci U S A
PubMed ID30598453
PubMed Central IDPMC6338849
Grant ListR01 GM107036 / GM / NIGMS NIH HHS / United States