5m3e | pdb_00005m3e
Macrodomain of Thermus aquaticus DarG in complex with ADP-ribose
Structural highlights
FunctionDARG_THEA5 Antitoxin component of a hybrid type II/IV toxin-antitoxin (TA) system. De-ADP-ribosylates DNA modified on thymidine by its cognate toxin DarT, which neutralizes the activity of cognate toxin DarT. Upon expression in E.coli neutralizes the effect of cognate toxin DarT (PubMed:27939941). Upon expression in M.tuberculosis neutralizes the toxic effects of endogenous DarT (PubMed:32634279).[1] [2] Publication Abstract from PubMedThe discovery and study of toxin-antitoxin (TA) systems helps us advance our understanding of the strategies prokaryotes employ to regulate cellular processes related to the general stress response, such as defense against phages, growth control, biofilm formation, persistence, and programmed cell death. Here we identify and characterize a TA system found in various bacteria, including the global pathogen Mycobacterium tuberculosis. The toxin of the system (DarT) is a domain of unknown function (DUF) 4433, and the antitoxin (DarG) a macrodomain protein. We demonstrate that DarT is an enzyme that specifically modifies thymidines on single-stranded DNA in a sequence-specific manner by a nucleotide-type modification called ADP-ribosylation. We also show that this modification can be removed by DarG. Our results provide an example of reversible DNA ADP-ribosylation, and we anticipate potential therapeutic benefits by targeting this enzyme-enzyme TA system in bacterial pathogens such as M. tuberculosis. The Toxin-Antitoxin System DarTG Catalyzes Reversible ADP-Ribosylation of DNA.,Jankevicius G, Ariza A, Ahel M, Ahel I Mol Cell. 2016 Dec 15;64(6):1109-1116. doi: 10.1016/j.molcel.2016.11.014. Epub, 2016 Dec 8. PMID:27939941[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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