PDBsum entry 1dma

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Adp-ribosylation PDB id
Protein chains
204 a.a.
189 a.a.
NCA ×2
Waters ×33
PDB id:
Name: Adp-ribosylation
Title: Domain iii of pseudomonas aeruginosa exotoxin complexed with nicotinamide and amp
Structure: Exotoxin a. Chain: a, b. Engineered: yes
Source: Pseudomonas aeruginosa. Organism_taxid: 287. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Tetramer (from PQS)
2.50Å     R-factor:   0.195     R-free:   0.265
Authors: M.Li,F.Dyda,I.Benhar,I.Pastan,D.Davies
Key ref: M.Li et al. (1995). The crystal structure of Pseudomonas aeruginosa exotoxin domain III with nicotinamide and AMP: conformational differences with the intact exotoxin. Proc Natl Acad Sci U S A, 92, 9308-9312. PubMed id: 7568123 DOI: 10.1073/pnas.92.20.9308
28-Apr-95     Release date:   15-Sep-95    
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Protein chain
Pfam   ArchSchema ?
P11439  (TOXA_PSEAE) -  Exotoxin A
638 a.a.
204 a.a.*
Protein chain
Pfam   ArchSchema ?
P11439  (TOXA_PSEAE) -  Exotoxin A
638 a.a.
189 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chains A, B: E.C.  - NAD(+)--diphthamide ADP-ribosyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: NAD+ + diphthamide-[translation elongation factor 2] = nicotinamide + N-(ADP-D-ribosyl)diphthamide-[translation elongation factor 2]
+ diphthamide-[translation elongation factor 2]
= nicotinamide
+ N-(ADP-D-ribosyl)diphthamide-[translation elongation factor 2]
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biochemical function     NAD+-diphthamide ADP-ribosyltransferase activity     1 term  


    Added reference    
DOI no: 10.1073/pnas.92.20.9308 Proc Natl Acad Sci U S A 92:9308-9312 (1995)
PubMed id: 7568123  
The crystal structure of Pseudomonas aeruginosa exotoxin domain III with nicotinamide and AMP: conformational differences with the intact exotoxin.
M.Li, F.Dyda, I.Benhar, I.Pastan, D.R.Davies.
Domain III of Pseudomonas aeruginosa exotoxin A catalyses the transfer of ADP-ribose from NAD to a modified histidine residue of elongation factor 2 in eukaryotic cells, thus inactivating elongation factor 2. This domain III is inactive in the intact toxin but is active in the isolated form. We report here the 2.5-A crystal structure of this isolated domain crystallized in the presence of NAD and compare it with the corresponding structure in the intact Pseudomonas aeruginosa exotoxin A. We observe a significant conformational difference in the active site region from Arg-458 to Asp-463. Contacts with part of domain II in the intact toxin prevent the adoption of the isolated domain conformation and provide a structural explanation for the observed inactivity. Additional electron density in the active site region corresponds to separate AMP and nicotinamide and indicates that the NAD has been hydrolyzed. The structure has been compared with the catalytic domain of the diphtheria toxin, which was crystallized with ApUp.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20106667 M.O.Hottiger, P.O.Hassa, B.Lüscher, H.Schüler, and F.Koch-Nolte (2010).
Toward a unified nomenclature for mammalian ADP-ribosyltransferases.
  Trends Biochem Sci, 35, 208-219.  
19344187 R.J.Kreitman (2009).
Recombinant immunotoxins containing truncated bacterial toxins for the treatment of hematologic malignancies.
  BioDrugs, 23, 1.  
18583986 R.Jørgensen, Y.Wang, D.Visschedyk, and A.R.Merrill (2008).
The nature and character of the transition state for the ADP-ribosyltransferase reaction.
  EMBO Rep, 9, 802-809.
PDB codes: 2zit 3b78 3b82 3b8h
  17641067 D.Baatar, P.Olkhanud, D.Newton, K.Sumitomo, and A.Biragyn (2007).
CCR4-expressing T cell tumors can be specifically controlled via delivery of toxins to chemokine receptors.
  J Immunol, 179, 1996-2004.  
16406634 S.P.Yates, R.Jørgensen, G.R.Andersen, and A.R.Merrill (2006).
Stealth and mimicry by deadly bacterial toxins.
  Trends Biochem Sci, 31, 123-133.  
15869381 D.Davies, and D.Davies (2005).
A quiet life with proteins.
  Annu Rev Biophys Biomol Struct, 34, 1.  
16202152 H.Otto, P.A.Reche, F.Bazan, K.Dittmar, F.Haag, and F.Koch-Nolte (2005).
In silico characterization of the family of PARP-like poly(ADP-ribosyl)transferases (pARTs).
  BMC Genomics, 6, 139.  
12583902 C.Thompson, A.R.Merrill, and D.Mangroo (2003).
Identification of peptide inhibitors of Pseudomonas aeruginosa exotoxin A function using a yeast two-hybrid approach.
  FEMS Microbiol Lett, 218, 85-92.  
11513605 F.Mohammadi, G.A.Prentice, and A.R.Merrill (2001).
Protein-protein interaction using tryptophan analogues: novel spectroscopic probes for toxin-elongation factor-2 interactions.
  Biochemistry, 40, 10273-10283.  
10713991 K.A.Denessiouk, and M.S.Johnson (2000).
When fold is not important: a common structural framework for adenine and AMP binding in 12 unrelated protein families.
  Proteins, 38, 310-326.  
10097145 R.Baluna, J.Rizo, B.E.Gordon, V.Ghetie, and E.S.Vitetta (1999).
Evidence for a structural motif in toxins and interleukin-2 that may be responsible for binding to endothelial cells and initiating vascular leak syndrome.
  Proc Natl Acad Sci U S A, 96, 3957-3962.  
10837618 I.Pastan, and R.J.Kreitman (1998).
Immunotoxins for targeted cancer therapy.
  Adv Drug Deliv Rev, 31, 53-88.  
9209499 D.M.Roscoe, L.H.Pai, and I.Pastan (1997).
Identification of epitopes on a mutant form of Pseudomonas exotoxin using serum from humans treated with Pseudomonas exotoxin containing immunotoxins.
  Eur J Immunol, 27, 1459-1468.  
9315851 V.Rolli, M.O'Farrell, J.Ménissier-de Murcia, and Murcia (1997).
Random mutagenesis of the poly(ADP-ribose) polymerase catalytic domain reveals amino acids involved in polymer branching.
  Biochemistry, 36, 12147-12154.  
8755499 A.Ruf, J.Mennissier de Murcia, Murcia, and G.E.Schulz (1996).
Structure of the catalytic fragment of poly(AD-ribose) polymerase from chicken.
  Proc Natl Acad Sci U S A, 93, 7481-7485.
PDB codes: 1paw 1pax
8703907 B.K.Beattie, and A.R.Merrill (1996).
In vitro enzyme activation and folded stability of Pseudomonas aeruginosa exotoxin A and its C-terminal peptide.
  Biochemistry, 35, 9042-9051.  
8952460 B.K.Beattie, G.A.Prentice, and A.R.Merrill (1996).
Investigation into the catalytic role for the tryptophan residues within domain III of Pseudomonas aeruginosa exotoxin A.
  Biochemistry, 35, 15134-15142.  
8805549 F.van den Akker, S.Sarfaty, E.M.Twiddy, T.D.Connell, R.K.Holmes, and W.G.Hol (1996).
Crystal structure of a new heat-labile enterotoxin, LT-IIb.
  Structure, 4, 665-678.
PDB code: 1tii
8901875 G.S.Prasad, D.E.McRee, E.A.Stura, D.G.Levitt, H.C.Lee, and C.D.Stout (1996).
Crystal structure of Aplysia ADP ribosyl cyclase, a homologue of the bifunctional ectozyme CD38.
  Nat Struct Biol, 3, 957-964.
PDB code: 1lbe
8692916 M.Li, F.Dyda, I.Benhar, I.Pastan, and D.R.Davies (1996).
Crystal structure of the catalytic domain of Pseudomonas exotoxin A complexed with a nicotinamide adenine dinucleotide analog: implications for the activation process and for ADP ribosylation.
  Proc Natl Acad Sci U S A, 93, 6902-6906.
PDB code: 1aer
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