PDBsum entry 1ddt

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Toxin PDB id
Protein chain
523 a.a.
Waters ×405
PDB id:
Name: Toxin
Title: The refined structure of dimeric diphtheria toxin at 2.0 ang resolution
Structure: Diphtheria toxin. Chain: a. Engineered: yes
Source: Corynephage beta. Organism_taxid: 10703
Biol. unit: Dimer (from PQS)
2.00Å     R-factor:   0.195    
Authors: M.J.Bennett,D.Eisenberg
Key ref: M.J.Bennett et al. (1994). Refined structure of dimeric diphtheria toxin at 2.0 A resolution. Protein Sci, 3, 1444-1463. PubMed id: 7833807 DOI: 10.1002/pro.5560030911
01-Mar-94     Release date:   31-Jul-94    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P00588  (DTX_CORBE) -  Diphtheria toxin
567 a.a.
523 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: 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!
  Cellular component     extracellular region   1 term 
  Biological process     metabolic process   2 terms 
  Biochemical function     transferase activity     3 terms  


    Added reference    
DOI no: 10.1002/pro.5560030911 Protein Sci 3:1444-1463 (1994)
PubMed id: 7833807  
Refined structure of dimeric diphtheria toxin at 2.0 A resolution.
M.J.Bennett, S.Choe, D.Eisenberg.
The refined structure of dimeric diphtheria toxin (DT) at 2.0 A resolution, based on 37,727 unique reflections (F > 1 sigma (F)), yields a final R factor of 19.5% with a model obeying standard geometry. The refined model consists of 523 amino acid residues, 1 molecule of the bound dinucleotide inhibitor adenylyl 3'-5' uridine 3' monophosphate (ApUp), and 405 well-ordered water molecules. The 2.0-A refined model reveals that the binding motif for ApUp includes residues in the catalytic and receptor-binding domains and is different from the Rossmann dinucleotide-binding fold. ApUp is bound in part by a long loop (residues 34-52) that crosses the active site. Several residues in the active site were previously identified as NAD-binding residues. Glu 148, previously identified as playing a catalytic role in ADP-ribosylation of elongation factor 2 by DT, is about 5 A from uracil in ApUp. The trigger for insertion of the transmembrane domain of DT into the endosomal membrane at low pH may involve 3 intradomain and 4 interdomain salt bridges that will be weakened at low pH by protonation of their acidic residues. The refined model also reveals that each molecule in dimeric DT has an "open" structure unlike most globular proteins, which we call an open monomer. Two open monomers interact by "domain swapping" to form a compact, globular dimeric DT structure. The possibility that the open monomer resembles a membrane insertion intermediate is discussed.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20976204 C.H.Chu, W.C.Lo, H.W.Wang, Y.C.Hsu, J.K.Hwang, P.C.Lyu, T.W.Pai, and C.Y.Tang (2010).
Detection and alignment of 3D domain swapping proteins using angle-distance image-based secondary structural matching techniques.
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20136512 J.F.Collet, and J.Messens (2010).
Structure, function, and mechanism of thioredoxin proteins.
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  20634983 K.Shameer, G.Pugalenthi, K.K.Kandaswamy, P.N.Suganthan, G.Archunan, and R.Sowdhamini (2010).
Insights into Protein Sequence and Structure-Derived Features Mediating 3D Domain Swapping Mechanism using Support Vector Machine Based Approach.
  Bioinform Biol Insights, 4, 33-42.  
19634988 M.A.Wouters, S.W.Fan, and N.L.Haworth (2010).
Disulfides as redox switches: from molecular mechanisms to functional significance.
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20050921 P.Man, C.Montagner, H.Vitrac, D.Kavan, S.Pichard, D.Gillet, E.Forest, and V.Forge (2010).
Accessibility changes within diphtheria toxin T domain when in the functional molten globule state, as determined using hydrogen/deuterium exchange measurements.
  FEBS J, 277, 653-662.  
20091872 R.P.Nagarkar, R.A.Hule, D.J.Pochan, and J.P.Schneider (2010).
Domain swapping in materials design.
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19263489 C.Ercole, R.A.Colamarino, E.Pizzo, F.Fogolari, R.Spadaccini, and D.Picone (2009).
Comparison of the structural and functional properties of RNase A and BS-RNase: A stepwise mutagenesis approach.
  Biopolymers, 91, 1009-1017.  
19475664 H.Dvir, M.E.Lundberg, S.K.Maji, R.Riek, and S.Choe (2009).
Mistic: cellular localization, solution behavior, polymerization, and fibril formation.
  Protein Sci, 18, 1564-1570.  
18055530 M.S.Kent, H.Yim, J.K.Murton, S.Satija, J.Majewski, and I.Kuzmenko (2008).
Oligomerization of membrane-bound diphtheria toxin (CRM197) facilitates a transition to the open form and deep insertion.
  Biophys J, 94, 2115-2127.  
18310255 M.V.Rodnin, Y.O.Posokhov, C.Contino-Pépin, J.Brettmann, A.Kyrychenko, S.S.Palchevskyy, B.Pucci, and A.S.Ladokhin (2008).
Interactions of fluorinated surfactants with diphtheria toxin T-domain: testing new media for studies of membrane proteins.
  Biophys J, 94, 4348-4357.  
18678276 S.Potala, S.K.Sahoo, and R.S.Verma (2008).
Targeted therapy of cancer using diphtheria toxin-derived immunotoxins.
  Drug Discov Today, 13, 807-815.  
17466257 A.P.Benfield, B.B.Whiddon, J.H.Clements, and S.F.Martin (2007).
Structural and energetic aspects of Grb2-SH2 domain-swapping.
  Arch Biochem Biophys, 462, 47-53.
PDB codes: 2h46 2h5k
17242377 G.Vernier, A.Chenal, H.Vitrac, R.Barumandzadhe, C.Montagner, and V.Forge (2007).
Interactions of apomyoglobin with membranes: mechanisms and effects on heme uptake.
  Protein Sci, 16, 391-400.  
17582168 L.M.Chavas, S.Torii, H.Kamikubo, M.Kawasaki, K.Ihara, R.Kato, M.Kataoka, T.Izumi, and S.Wakatsuki (2007).
Structure of the small GTPase Rab27b shows an unexpected swapped dimer.
  Acta Crystallogr D Biol Crystallogr, 63, 769-779.
PDB codes: 2iey 2iez 2if0
16447281 G.Song, and R.L.Jernigan (2006).
An enhanced elastic network model to represent the motions of domain-swapped proteins.
  Proteins, 63, 197-209.  
16563740 S.J.Tilley, and H.R.Saibil (2006).
The mechanism of pore formation by bacterial toxins.
  Curr Opin Struct Biol, 16, 230-236.  
15596505 A.Merlino, M.A.Ceruso, L.Vitagliano, and L.Mazzarella (2005).
Open interface and large quaternary structure movements in 3D domain swapped proteins: insights from molecular dynamics simulations of the C-terminal swapped dimer of ribonuclease A.
  Biophys J, 88, 2003-2012.  
15341731 A.U.Singer, D.Desveaux, L.Betts, J.H.Chang, Z.Nimchuk, S.R.Grant, J.L.Dangl, and J.Sondek (2004).
Crystal structures of the type III effector protein AvrPphF and its chaperone reveal residues required for plant pathogenesis.
  Structure, 12, 1669-1681.
PDB codes: 1s21 1s28
14696043 M.A.Wouters, K.K.Lau, and P.J.Hogg (2004).
Cross-strand disulphides in cell entry proteins: poised to act.
  Bioessays, 26, 73-79.  
15103625 M.Stehr, and Y.Lindqvist (2004).
NrdH-redoxin of Corynebacterium ammoniagenes forms a domain-swapped dimer.
  Proteins, 55, 613-619.
PDB code: 1r7h
15189881 S.Kundu, and R.L.Jernigan (2004).
Molecular mechanism of domain swapping in proteins: an analysis of slower motions.
  Biophys J, 86, 3846-3854.  
12121644 E.S.Stavridi, Y.Huyen, I.R.Loreto, D.M.Scolnick, T.D.Halazonetis, N.P.Pavletich, and P.D.Jeffrey (2002).
Crystal structure of the FHA domain of the Chfr mitotic checkpoint protein and its complex with tungstate.
  Structure, 10, 891-899.
PDB codes: 1lgp 1lgq
12414710 H.H.Gan, R.A.Perlow, S.Roy, J.Ko, M.Wu, J.Huang, S.Yan, A.Nicoletta, J.Vafai, D.Sun, L.Wang, J.E.Noah, S.Pasquali, and T.Schlick (2002).
Analysis of protein sequence/structure similarity relationships.
  Biophys J, 83, 2781-2791.  
12021428 Y.Liu, and D.Eisenberg (2002).
3D domain swapping: as domains continue to swap.
  Protein Sci, 11, 1285-1299.  
11344301 F.Rousseau, J.W.Schymkowitz, H.R.Wilkinson, and L.S.Itzhaki (2001).
Three-dimensional domain swapping in p13suc1 occurs in the unfolded state and is controlled by conserved proline residues.
  Proc Natl Acad Sci U S A, 98, 5596-5601.  
11709166 J.W.O'Neill, D.E.Kim, K.Johnsen, D.Baker, and K.Y.Zhang (2001).
Single-site mutations induce 3D domain swapping in the B1 domain of protein L from Peptostreptococcus magnus.
  Structure, 9, 1017-1027.
PDB codes: 1k50 1k51 1k52 1k53
11573096 J.W.Schymkowitz, F.Rousseau, H.R.Wilkinson, A.Friedler, and L.S.Itzhaki (2001).
Observation of signal transduction in three-dimensional domain swapping.
  Nat Struct Biol, 8, 888-892.  
11123917 B.Steere, and D.Eisenberg (2000).
Characterization of high-order diphtheria toxin oligomers.
  Biochemistry, 39, 15901-15909.  
10657208 R.K.Holmes (2000).
Biology and molecular epidemiology of diphtheria toxin and the tox gene.
  J Infect Dis, 181, S156-S167.  
  10496871 C.Fromen-Romano, P.Drevet, A.Robert, A.Ménez, and M.Léonetti (1999).
Recombinant Staphylococcus strains as live vectors for the induction of neutralizing anti-diphtheria toxin antisera.
  Infect Immun, 67, 5007-5011.  
  10211836 D.R.Westhead, T.W.Slidel, T.P.Flores, and J.M.Thornton (1999).
Protein structural topology: Automated analysis and diagrammatic representation.
  Protein Sci, 8, 897-904.  
9893993 J.Ren, J.C.Sharpe, R.J.Collier, and E.London (1999).
Membrane translocation of charged residues at the tips of hydrophobic helices in the T domain of diphtheria toxin.
  Biochemistry, 38, 976-984.  
9671502 A.P.Saint-Jean, K.R.Phillips, D.J.Creighton, and M.J.Stone (1998).
Active monomeric and dimeric forms of Pseudomonas putida glyoxalase I: evidence for 3D domain swapping.
  Biochemistry, 37, 10345-10353.  
9521710 A.Ruf, Murcia, and G.E.Schulz (1998).
Inhibitor and NAD+ binding to poly(ADP-ribose) polymerase as derived from crystal structures and homology modeling.
  Biochemistry, 37, 3893-3900.
PDB codes: 2paw 2pax 3pax 4pax
9789264 G.Del Giudice, M.Pizza, and R.Rappuoli (1998).
Molecular basis of vaccination.
  Mol Aspects Med, 19, 1.  
  9453589 K.Lobeck, P.Drevet, M.Léonetti, C.Fromen-Romano, F.Ducancel, E.Lajeunesse, C.Lemaire, and A.Ménez (1998).
Towards a recombinant vaccine against diphtheria toxin.
  Infect Immun, 66, 418-423.  
9485477 R.Landgraf, M.Pegram, D.J.Slamon, and D.Eisenberg (1998).
Cytotoxicity and specificity of directed toxins composed of diphtheria toxin and the EGF-like domain of heregulin beta1.
  Biochemistry, 37, 3220-3228.  
9539728 S.D.Zakharov, M.Lindeberg, Y.Griko, Z.Salamon, G.Tollin, F.G.Prendergast, and W.A.Cramer (1998).
Membrane-bound state of the colicin E1 channel domain as an extended two-dimensional helical array.
  Proc Natl Acad Sci U S A, 95, 4282-4287.  
9922159 S.E.Malenbaum, R.J.Collier, and E.London (1998).
Membrane topography of the T domain of diphtheria toxin probed with single tryptophan mutants.
  Biochemistry, 37, 17915-17922.  
9012663 C.E.Bell, and D.Eisenberg (1997).
Crystal structure of nucleotide-free diphtheria toxin.
  Biochemistry, 36, 481-488.
PDB code: 1sgk
9659904 G.V.Louie, W.Yang, M.E.Bowman, and S.Choe (1997).
Crystal structure of the complex of diphtheria toxin with an extracellular fragment of its receptor.
  Mol Cell, 1, 67-78.
PDB code: 1xdt
9083108 M.Bergdoll, M.H.Remy, C.Cagnon, J.M.Masson, and P.Dumas (1997).
Proline-dependent oligomerization with arm exchange.
  Structure, 5, 391-401.  
  9276751 P.D.Huynh, C.Cui, H.Zhan, K.J.Oh, R.J.Collier, and A.Finkelstein (1997).
Probing the structure of the diphtheria toxin channel. Reactivity in planar lipid bilayer membranes of cysteine-substituted mutant channels with methanethiosulfonate derivatives.
  J Gen Physiol, 110, 229-242.  
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
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.  
8573568 C.E.Bell, and D.Eisenberg (1996).
Crystal structure of diphtheria toxin bound to nicotinamide adenine dinucleotide.
  Biochemistry, 35, 1137-1149.
PDB code: 1tox
7648317 E.A.Merritt, and W.G.Hol (1995).
AB5 toxins.
  Curr Opin Struct Biol, 5, 165-171.  
  8580836 M.J.Bennett, M.P.Schlunegger, and D.Eisenberg (1995).
3D domain swapping: a mechanism for oligomer assembly.
  Protein Sci, 4, 2455-2468.  
8566002 R.Raju, D.Navaneetham, D.Okita, B.Diethelm-Okita, D.McCormick, and B.M.Conti-Fine (1995).
Epitopes for human CD4+ cells on diphtheria toxin: structural features of sequence segments forming epitopes recognized by most subjects.
  Eur J Immunol, 25, 3207-3214.  
  7833808 M.J.Bennett, and D.Eisenberg (1994).
Refined structure of monomeric diphtheria toxin at 2.3 A resolution.
  Protein Sci, 3, 1464-1475.
PDB code: 1mdt
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