DB code: D00463

RLCP classification 3.955.50030.967 : Transfer
CATH domain 3.90.176.10 : Toxin ADP-ribosyltransferase; Chain A, domain 1
3.90.176.10 : Toxin ADP-ribosyltransferase; Chain A, domain 1 Catalytic domain
E.C. 2.4.2.30
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Pfam
Q844J9
Vip2Ac
PF03496 (ADPrib_exo_Tox)
[Graphical View]

KEGG enzyme 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

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
Q844J9 Q844J9_BACTU

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C00003 C03245 C00153 C03245 C00080
E.C.
Compound NAD+ (ADP-D-ribosyl)n-acceptor Nicotinamide (ADP-D-ribosyl)n+1-acceptor H+
Type amide group,amine group,nucleotide carbohydrate,nucleotide ,peptide/protein amide group,aromatic ring (with nitrogen atoms) carbohydrate,nucleotide ,peptide/protein others
ChEBI 15846
17154
15378
PubChem 5893
936
1038
1qs1A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1qs1B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1qs1C01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1qs1D01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1qs2A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1qs1A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1qs1B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1qs1C02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1qs1D02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1qs2A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:NAD Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [7]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1qs1A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1qs1B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1qs1C01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1qs1D01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1qs2A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1qs1A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 349;ARG 400;GLU 426;GLU 428
1qs1B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 1349;ARG 1400;GLU 1426;GLU 1428
1qs1C02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 2349;ARG 2400;GLU 2426;GLU 2428
1qs1D02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 3349;ARG 3400;GLU 3426;GLU 3428
1qs2A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 349;ARG 400;GLU 426;GLU 428

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[7]
Fig. 3c, p.935

References
[1]
Resource
Comments
Medline ID
PubMed ID 1628500
Journal Curr Top Microbiol Immunol
Year 1992
Volume 175
Pages 97-113
Authors Aktories K, Wille M, Just I
Title Clostridial actin-ADP-ribosylating toxins.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 8898093
Journal FEBS Lett
Year 1996
Volume 395
Pages 191-4
Authors Perelle S, Domenighini M, Popoff MR
Title Evidence that Arg-295, Glu-378, and Glu-380 are active-site residues of the ADP-ribosyltransferase activity of iota toxin.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 9193636
Journal Adv Exp Med Biol
Year 1997
Volume 419
Pages 53-60
Authors Aktories K
Title Identification of the catalytic site of clostridial ADP-ribosyltransferases.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 9792657
Journal J Biol Chem
Year 1998
Volume 273
Pages 29506-11
Authors Barth H, Preiss JC, Hofmann F, Aktories K
Title Characterization of the catalytic site of the ADP-ribosyltransferase Clostridium botulinum C2 toxin by site-directed mutagenesis.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 10735850
Journal J Bacteriol
Year 2000
Volume 182
Pages 2096-103
Authors Nagahama M, Sakaguchi Y, Kobayashi K, Ochi S, Sakurai J
Title Characterization of the enzymatic component of Clostridium perfringens iota-toxin.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 11890553
Journal Int J Med Microbiol
Year 2002
Volume 291
Pages 523-9
Authors Han S, Tainer JA
Title The ARTT motif and a unified structural understanding of substrate recognition in ADP-ribosylating bacterial toxins and eukaryotic ADP-ribosyltransferases.
Related PDB
Related UniProtKB
[7]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10504727
Journal Nat Struct Biol
Year 1999
Volume 6
Pages 932-6
Authors Han S, Craig JA, Putnam CD, Carozzi NB, Tainer JA
Title Evolution and mechanism from structures of an ADP-ribosylating toxin and NAD complex
Related PDB 1qs1 1qs2
Related UniProtKB

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.

Created Updated
2004-03-25 2009-02-26