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ParST is a widespread toxin–antitoxin module that targets nucleotide metabolism
- Source :
- Proceedings of the National Academy of Sciences. 116:826-834
- Publication Year :
- 2018
- Publisher :
- Proceedings of the National Academy of Sciences, 2018.
-
Abstract
- 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.
- Subjects :
- medicine.disease_cause
03 medical and health sciences
chemistry.chemical_compound
Escherichia coli
Ribose-Phosphate Pyrophosphokinase
RefSeq
medicine
Amino Acid Sequence
030304 developmental biology
ADP Ribose Transferases
chemistry.chemical_classification
0303 health sciences
Crystallography
Multidisciplinary
biology
Nucleotides
030306 microbiology
Toxin
Phosphoribosyl pyrophosphate
Toxin-Antitoxin Systems
biology.organism_classification
Toxin-antitoxin system
Sphingomonadaceae
Enzyme
PNAS Plus
chemistry
Biochemistry
ADP-ribosylation
Antitoxin
Bacteria
Subjects
Details
- ISSN :
- 10916490 and 00278424
- Volume :
- 116
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences
- Accession number :
- edsair.doi.dedup.....183f15219809ab4bddb3b43df999b081