EzCatDB: D00463
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DB codeD00463
RLCP classification3.955.50030.967 : Transfer
CATH domainDomain 13.90.176.10 : Toxin ADP-ribosyltransferase; Chain A, domain 1
Domain 23.90.176.10 : Toxin ADP-ribosyltransferase; Chain A, domain 1Catalytic domain
E.C.2.4.2.30


Enzyme Name
UniProtKBKEGG

Q844J9
Protein name
NAD+ ADP-ribosyltransferase
poly(ADP-ribose) synthase
ADP-ribosyltransferase (polymerizing)
NAD ADP-ribosyltransferase
PARP
PARP-1
NAD+:poly(adenine-diphosphate-D-ribosyl)-acceptorADP-D-ribosyl-transferase (incorrect)
NAD+:poly(adenosine-diphosphate-D-ribosyl)-acceptorADP-D-ribosyl-transferase
SynonymsVip2Ac
PfamPF03496 (ADPrib_exo_Tox)
[Graphical view]


UniProtKB:Accession NumberQ844J9
Entry nameQ844J9_BACTU
Activity
Subunit
Subcellular location
Cofactor

Compound table: links to PDB-related databases & PoSSuM

SubstratesProducts
KEGG-idC00003C03245C00153C03245C00080
CompoundNAD+(ADP-D-ribosyl)n-acceptorNicotinamide(ADP-D-ribosyl)n+1-acceptorH+
Typeamide group,amine group,nucleotidecarbohydrate,nucleotide,peptide/proteinamide group,aromatic ring (with nitrogen atoms)carbohydrate,nucleotide,peptide/proteinothers
ChEBI15846

17154

15378
PubChem5893

936

1038
             
1qs1A01UnboundUnboundUnboundUnbound 
1qs1B01UnboundUnboundUnboundUnbound 
1qs1C01UnboundUnboundUnboundUnbound 
1qs1D01UnboundUnboundUnboundUnbound 
1qs2A01UnboundUnboundUnboundUnbound 
1qs1A02UnboundUnboundUnboundUnbound 
1qs1B02UnboundUnboundUnboundUnbound 
1qs1C02UnboundUnboundUnboundUnbound 
1qs1D02UnboundUnboundUnboundUnbound 
1qs2A02Bound:NADUnboundUnboundUnbound 

Active-site residues
resource
literature [7]
pdbCatalytic residues
         
1qs1A01 
1qs1B01 
1qs1C01 
1qs1D01 
1qs2A01 
1qs1A02ARG  349;ARG  400;GLU  426;GLU  428
1qs1B02ARG 1349;ARG 1400;GLU 1426;GLU 1428
1qs1C02ARG 2349;ARG 2400;GLU 2426;GLU 2428
1qs1D02ARG 3349;ARG 3400;GLU 3426;GLU 3428
1qs2A02ARG  349;ARG  400;GLU  426;GLU  428

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[7]Fig. 3c, p.935

references
[1]
PubMed ID1628500
JournalCurr Top Microbiol Immunol
Year1992
Volume175
Pages97-113
AuthorsAktories K, Wille M, Just I
TitleClostridial actin-ADP-ribosylating toxins.
[2]
PubMed ID8898093
JournalFEBS Lett
Year1996
Volume395
Pages191-4
AuthorsPerelle S, Domenighini M, Popoff MR
TitleEvidence that Arg-295, Glu-378, and Glu-380 are active-site residues of the ADP-ribosyltransferase activity of iota toxin.
[3]
PubMed ID9193636
JournalAdv Exp Med Biol
Year1997
Volume419
Pages53-60
AuthorsAktories K
TitleIdentification of the catalytic site of clostridial ADP-ribosyltransferases.
[4]
PubMed ID9792657
JournalJ Biol Chem
Year1998
Volume273
Pages29506-11
AuthorsBarth H, Preiss JC, Hofmann F, Aktories K
TitleCharacterization of the catalytic site of the ADP-ribosyltransferase Clostridium botulinum C2 toxin by site-directed mutagenesis.
[5]
PubMed ID10735850
JournalJ Bacteriol
Year2000
Volume182
Pages2096-103
AuthorsNagahama M, Sakaguchi Y, Kobayashi K, Ochi S, Sakurai J
TitleCharacterization of the enzymatic component of Clostridium perfringens iota-toxin.
[6]
PubMed ID11890553
JournalInt J Med Microbiol
Year2002
Volume291
Pages523-9
AuthorsHan S, Tainer JA
TitleThe ARTT motif and a unified structural understanding of substrate recognition in ADP-ribosylating bacterial toxins and eukaryotic ADP-ribosyltransferases.
[7]
CommentsX-ray crystallography
PubMed ID10504727
JournalNat Struct Biol
Year1999
Volume6
Pages932-6
AuthorsHan S, Craig JA, Putnam CD, Carozzi NB, Tainer JA
TitleEvolution and mechanism from structures of an ADP-ribosylating toxin and NAD complex
Related PDB1qs1,1qs2

comments
This entry includes VIP2 and C2 toxin, whilst the counterpart from Diphtheria toxin is deposited in another file T00039 (E.C. 2.4.2.36).
According to the literature [7], the catalytic reaction proceeds by SN1-like mechanism, as follows:
(1) Breakage of C1'-N glycosylic bond occurs, leading to the oxocarbenium transtion-state, which is stablized by Glu428, Arg349 and Arg400. Here, the negative charge of Glu428 sidechain increases electronic density on the nicotinamide ring, and stabilizes the oxocarbenium ion formed on the sugar moiety. On the other hand, Arg349 and Arg400 stabilize the negative charge on the phosphate group of NAD, which in turn stabilizes the leaving nicotinamide ring.
(2) Glu426 acts as a general base, to activate the acceptor group, Arg177 of Actin protein, by deprotonating it.
(3) The activated Arg177 makes a nucleophilic attack on the C1' atom of the oxocarbenium ion, to complete the reaction.

createdupdated
2004-03-252009-02-26


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