ADP-ribosylation is a protein modification process that occurs widely in
pathogenic mechanisms, intracellular signaling systems, DNA repair, and cell
division. The reaction is catalyzed by ADP-ribosyltransferases which transfer
the ADP-ribose moiety of NAD to a target protein with nicotinamide release.
This stereospecific reaction is catalyzed by mono- and poly-ADP-ribosyltransferases (mARTs and pARTs). mARTs catalyze the transfer of a single
ADP-ribose moiety onto a specific amino acid side chain of a target protein;
pARTs (also designated poly-ADP-ribose-polymerases or PARPs), additionally can
catalyze the elongation and branching of ADP-ribose units on ADP-ribosylated
targets (see <PDOC51059>). The mART subfamily includes many well-known
bacterial toxins as well as a number of mammalian and avian ecto-enzymes:
Clostridium botulinum C3 exoenzyme inactivates the small GTP-binding
protein family Rho by ADP-ribosylating asparagine 41, which depolymerizes
the actin cytoskeleton .
Clostridium botulinum C2 toxin is composed of the enzyme component C2-I,
which ADP-ribosylates actin, and the binding and translocation component
C2-II, responsible for the interaction with eukaryotic cell receptors and
the following endocytosis .
Clostridium perfringens type E Iota-toxin is an ADP-ribosylating toxin
(ADPRT) that ADP-ribosylates actin, which is lethal and dermonecrotic in
Salmonella typhimurium Mono(ADP-ribosyl)transferase SpvB, a virulence
Bacillus cereus vegetative insecticidal protein (VIP2), an insect-targeted
Bacillus cereus Certhrax Toxin, an Anthrax-related ADP-ribosyltransferase.
It has two domains, one that binds protective antigen and another that has
ADP-ribosyltransferase activity .
Pseudomonas syringae type III effector HopU1, a mono-ADP-ribosyltransferase
that is injected into plant cells by the type III protein secretion system.
Inside the plant cell it suppresses immunity by modifying RNA-binding
proteins including the glycine-rich RNA-binding protein GRP7 .
Xanthomonas axonopodis pv. citri (Xac) XopAI, a putative type III effector.
Iit has been suggested to be a pathogenicity factor for citrus canker.
XopAI uses an altered mART domain to bind its own N-terminal peptide
containing a conserved Arg residue .
Mammalian toxin-related ecto-ADP-ribosyltransferases family [Glowacki].
Most known mARTs transfer ADP-ribose onto arginine residues (see <PS01291>).
Some enzymatically inactive mART domains, for example, the N-terminal domains
of C2 and VIP2 toxins, have acquired a new, protein-binding function.
The mART domain adopts a mixed α/β-fold with a characteristic β-sandwich structure. Each domain core is formed mainly by perpendicular packing
of a five-stranded mixed β-sheet against a three-stranded antiparallel
β-sheet. The three-stranded sheet is flanked by four consecutive α-helices and the five-stranded sheet by an additional α-helix. A central
cleft, which is formed between the four consecutive α-helices and the
five-stranded β-sheet and lined by an α-helix and four β-strands,
forms the NAD binding pocket (see <PDB:1QS1>). Catalytically active TR mART
domains hallmark catalytic residues in the active site. Specifically, (i) a
catalytic Arg preceded by an aromatic residue aids in NAD(+) binding and
scaffolding of the active site, (ii) a Ser-Thr-Ser motif on a β-strand
stabilizes the NAD(+) binding site, (iii) the ADP-ribosyl-turn-turn (ARTT)
loop contains a catalytic Glu responsible for the ADP-ribosyltransferase
activity and a Gln/Glu two residues upstream that may participate in substrate
recognition, and (iv) a “phosphate-nicotinamide” (PN) loop contributes to
NAD(+) binding through hydrogen bonds with an Arg and aromatic residues.
The profile we developed covers the entire TR mART core domain.
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