6d0i | pdb_00006d0i
ParT: Prs ADP-ribosylating toxin bound to cognate antitoxin ParS. L48M ParT, SeMet-substituted complex.
Structural highlights
FunctionPART_SPHYB Toxic component of a type II toxin-antitoxin (TA) system. Expression in E.coli inhibits cell growth; bacteriostasis is neutralized by expression of cognate antitoxin ParS. ADP-ribosylates E.coli ribose-phosphate pyrophosphokinase (RPPK, prs) using NAD(+) in vitro; ADP-ribosylates RPPK on 'Lys-182' and 'Ser-202'. Cannot use NADP(+). Also auto-ADP-ribosylates in vitro; in the presence of RPPK auto-ADP-ribosylation decreases.[1] Publication Abstract from PubMedToxin-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 A. 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. ParST is a widespread toxin-antitoxin module that targets nucleotide metabolism.,Piscotta FJ, Jeffrey PD, Link AJ Proc Natl Acad Sci U S A. 2018 Dec 31. pii: 1814633116. doi:, 10.1073/pnas.1814633116. PMID:30598453[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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