{PDOC52018}
{PS52018; DART}
{BEGIN}
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* DNA ADP-ribosyl transferase (DarT) domain profile *
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ADP-ribosylation is  a chemical modification of macromolecules via transfer of
an ADP-ribose  (ADPr)  moiety  from  NAD(+)  onto  molecular  targets (usually
proteins). ADP-ribosyltransferases  use  NAD(+)  to  catalyse  substrate  ADP-
ribosylation, and  thereby  regulate cellular pathways or contribute to toxin-
mediated pathogenicity  of  bacteria.  Reversible  ADP-ribosylation  of DNA on
thymidine bases  occurs through the DarT-DarG toxin–antitoxin system, which is
found in   a   variety   of  bacteria  (including  global  pathogens  such  as
Mycobacterium tuberculosis,  enteropathogenic Escherichia coli and Pseudomonas
aeruginosa). The  bacterial  DNA  ADP-ribosyl  transferase (DarT) protein is a
toxin that  has  been  shown to transfer ADP-ribose from NAD(+) onto thymidine
bases present  in  single-stranded  DNA  (ssDNA) specifically at the four-base
motif TNTC,  and  to  have  no  activity  on  RNA  or protein targets. DarT is
controlled by its antitoxin DarG (for DNA ADP-ribosyl glycohydrolase) that can
strip off  the  ADP-ribosylation  and  consequently  abolish the growth arrest
caused by DarT in bacterial cells. In its N-terminal part, DarG contains a so-
called macro  domain  that  is  well  known  as  a module interacting with—and
frequently removing-ADP-ribosylation  (see  <PDOC51154>), while the C-terminal
region of the antitoxin does not display any known protein domains [1,2,3].

The DarT  domain  contains  a fold-stabilizing central six-stranded beta-sheet
core (see  <PDB:7OMZ>). The DNA target is bound within a groove that is highly
conserved among  members  of  the  DarT  family,  and lined up with a positive
electrostatic surface  generated by several basic residues. The nucleotides of
the DNA  target  span  the entire groove, with the thymidine targeted for ADP-
ribosylation pointing  orthogonally  to  the DNA backbone deep into the active
site of  DarT. DarT catalyses ADP-ribosylation of DNA by linking ADP-ribose at
the nicotinamide (NAM) ribose C1'' to the in-ring nitrogen N3 of the thymidine
base [1].

The profile we developed covers the entire DarT domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: February 2023 / Profile revised.

[ 1] Schuller M., Butler R.E., Ariza A., Tromans-Coia C., Jankevicius G.,
     Claridge T.D.W., Kendall S.L., Goh S., Stewart G.R., Ahel I.
     "Molecular basis for DarT ADP-ribosylation of a DNA base."
     Nature 596:597-602(2021).
     PubMed=34408320; DOI=10.1038/s41586-021-03825-4
[ 2] Harms A., Gerdes K.
     "Back to the Roots: Deep View into the Evolutionary History of
     ADP-Ribosylation  Opened by the DNA-Targeting Toxin-Antitoxin Module
     DarTG."
     Mol. Cell. 64:1020-1021(2016).
     PubMed=27984742; DOI=10.1016/j.molcel.2016.11.038
[ 3] Jankevicius G., Ariza A., Ahel M., Ahel I.
     "The Toxin-Antitoxin System DarTG Catalyzes Reversible
     ADP-Ribosylation of DNA."
     Mol. Cell. 64:1109-1116(2016).
     PubMed=27939941; DOI=10.1016/j.molcel.2016.11.014

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