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PDBsum entry 1d0h
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Toxin PDB id
1d0h

 

 

 

 

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Contents
Protein chain
441 a.a. *
Ligands
A2G ×2
SO4
Waters ×501
* Residue conservation analysis
PDB id:
1d0h
Name: Toxin
Title: The hc fragment of tetanus toxin complexed with n-acetyl-galactosamine
Structure: Protein (tetanus toxin hc). Chain: a. Fragment: c-terminal domain of heavy chain. Synonym: tentoxylysin. Engineered: yes. Mutation: yes
Source: Clostridium tetani. Organism_taxid: 1513. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.10Å     R-factor:   0.205     R-free:   0.270
Authors: P.Emsley,C.Fotinou,I.Black,N.F.Fairweather,I.G.Charles,C.Watts, E.Hewitt,N.W.Isaacs
Key ref:
P.Emsley et al. (2000). The structures of the H(C) fragment of tetanus toxin with carbohydrate subunit complexes provide insight into ganglioside binding. J Biol Chem, 275, 8889-8894. PubMed id: 10722735 DOI: 10.1074/jbc.275.12.8889
Date:
10-Sep-99     Release date:   27-Mar-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P04958  (TETX_CLOTE) -  Tetanus toxin from Clostridium tetani (strain Massachusetts / E88)
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1315 a.a.
441 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.4.24.68  - tentoxilysin.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Hydrolysis of 76-Gln-|-Phe-77 bond in synaptobrevin 2.
      Cofactor: Zn(2+)

 

 
DOI no: 10.1074/jbc.275.12.8889 J Biol Chem 275:8889-8894 (2000)
PubMed id: 10722735  
 
 
The structures of the H(C) fragment of tetanus toxin with carbohydrate subunit complexes provide insight into ganglioside binding.
P.Emsley, C.Fotinou, I.Black, N.F.Fairweather, I.G.Charles, C.Watts, E.Hewitt, N.W.Isaacs.
 
  ABSTRACT  
 
The entry of tetanus neurotoxin into neuronal cells proceeds through the initial binding of the toxin to gangliosides on the cell surface. The carboxyl-terminal fragment of the heavy chain of tetanus neurotoxin contains the ganglioside-binding site, which has not yet been fully characterized. The crystal structures of native H(C) and of H(C) soaked with carbohydrates reveal a number of binding sites and provide insight into the possible mode of ganglioside binding.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. The overall fold of TeNT H[C]. The protein is composed of two domains, a lentil lectin-like amino-terminal domain and a -trefoil carboxyl-terminal domain. 		Figure 5.
Fig. 5. A stereo view, in the same orientation as Fig. 1, of the positions of the carbohydrate units with respect to TeNT H[C]. The carbohydrate units bind in four distinct sites, and their positions and orientations make it unlikely that these would correspond to a single ganglioside binding to a single H[C] protein.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2000, 275, 8889-8894) copyright 2000.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21456874 T.Okada, and N.Minoura (2011).
Fluorescence emission and polarization analyses for evaluating binding of ruthenium metalloglycoclusters to lectins and tetanus toxin C-fragment.
  J Biomed Opt, 16, 037001.  
19757026 A.F.Bongat, R.Saksena, R.Adamo, Y.Fujimoto, Z.Shiokawa, D.C.Peterson, K.Fukase, W.F.Vann, and P.Kovác (2010).
Multimeric bivalent immunogens from recombinant tetanus toxin HC fragment, synthetic hexasaccharides, and a glycopeptide adjuvant.
  Glycoconj J, 27, 69-77.  
20704566 J.Strotmeier, K.Lee, A.K.Völker, S.Mahrhold, Y.Zong, J.Zeiser, J.Zhou, A.Pich, H.Bigalke, T.Binz, A.Rummel, and R.Jin (2010).
Botulinum neurotoxin serotype D attacks neurons via two carbohydrate-binding sites in a ganglioside-dependent manner.
  Biochem J, 431, 207-216.
PDB codes: 3obr 3obt
20413159 N.Scott, O.Qazi, M.J.Wright, N.F.Fairweather, and M.P.Deonarain (2010).
Characterisation of a panel of anti-tetanus toxin single-chain Fvs reveals cooperative binding.
  Mol Immunol, 47, 1931-1941.  
19650874 A.Rummel, K.Häfner, S.Mahrhold, N.Darashchonak, M.Holt, R.Jahn, S.Beermann, T.Karnath, H.Bigalke, and T.Binz (2009).
Botulinum neurotoxins C, E and F bind gangliosides via a conserved binding site prior to stimulation-dependent uptake with botulinum neurotoxin F utilising the three isoforms of SV2 as second receptor.
  J Neurochem, 110, 1942-1954.  
19602728 C.Chen, Z.Fu, J.J.Kim, J.T.Barbieri, and M.R.Baldwin (2009).
Gangliosides as high affinity receptors for tetanus neurotoxin.
  J Biol Chem, 284, 26569-26577.
PDB codes: 3hmy 3hn1
19824793 M.R.Popoff, and P.Bouvet (2009).
Clostridial toxins.
  Future Microbiol, 4, 1021-1064.  
17185412 A.Rummel, T.Eichner, T.Weil, T.Karnath, A.Gutcaits, S.Mahrhold, K.Sandhoff, R.L.Proia, K.R.Acharya, H.Bigalke, and T.Binz (2007).
Identification of the protein receptor binding site of botulinum neurotoxins B and G proves the double-receptor concept.
  Proc Natl Acad Sci U S A, 104, 359-364.  
17188834 T.Kohda, H.Ihara, Y.Seto, H.Tsutsuki, M.Mukamoto, and S.Kozaki (2007).
Differential contribution of the residues in C-terminal half of the heavy chain of botulinum neurotoxin type B to its binding to the ganglioside GT1b and the synaptotagmin 2/GT1b complex.
  Microb Pathog, 42, 72-79.  
16713287 M.C.Conway, R.M.Whittal, M.A.Baldwin, A.L.Burlingame, and R.Balhorn (2006).
Electrospray mass spectrometry of NeuAc oligomers associated with the C fragment of the tetanus toxin.
  J Am Soc Mass Spectrom, 17, 967-976.  
16431098 M.M.Ngundi, C.R.Taitt, and F.S.Ligler (2006).
Simultaneous determination of kinetic parameters for the binding of cholera toxin to immobilized sialic acid and monoclonal antibody using an array biosensor.
  Biosens Bioelectron, 22, 124-130.  
15946840 M.M.Ngundi, C.R.Taitt, S.A.McMurry, D.Kahne, and F.S.Ligler (2006).
Detection of bacterial toxins with monosaccharide arrays.
  Biosens Bioelectron, 21, 1195-1201.  
16861677 O.Qazi, D.Sesardic, R.Tierney, Z.Söderbäck, D.Crane, B.Bolgiano, and N.Fairweather (2006).
Reduction of the ganglioside binding activity of the tetanus toxin HC fragment destroys immunogenicity: implications for development of novel tetanus vaccines.
  Infect Immun, 74, 4884-4891.  
16574153 V.N.Kasho, I.N.Smirnova, and H.R.Kaback (2006).
Sequence alignment and homology threading reveals prokaryotic and eukaryotic proteins similar to lactose permease.
  J Mol Biol, 358, 1060-1070.  
16104015 S.Jayaraman, S.Eswaramoorthy, D.Kumaran, and S.Swaminathan (2005).
Common binding site for disialyllactose and tri-peptide in C-fragment of tetanus neurotoxin.
  Proteins, 61, 288-295.
PDB codes: 1yxw 1yyn
14731268 A.Rummel, S.Mahrhold, H.Bigalke, and T.Binz (2004).
The HCC-domain of botulinum neurotoxins A and B exhibits a singular ganglioside binding site displaying serotype specific carbohydrate interaction.
  Mol Microbiol, 51, 631-643.  
15381192 C.Montecucco, O.Rossetto, and G.Schiavo (2004).
Presynaptic receptor arrays for clostridial neurotoxins.
  Trends Microbiol, 12, 442-446.  
15382229 M.J.Bernett, T.Somasundaram, and M.Blaber (2004).
An atomic resolution structure for human fibroblast growth factor 1.
  Proteins, 57, 626-634.
PDB code: 1rg8
12794937 B.M.Paddle (2003).
Therapy and prophylaxis of inhaled biological toxins.
  J Appl Toxicol, 23, 139-170.  
13678859 G.Lalli, S.Bohnert, K.Deinhardt, C.Verastegui, and G.Schiavo (2003).
The journey of tetanus and botulinum neurotoxins in neurons.
  Trends Microbiol, 11, 431-437.  
14627732 S.R.Brych, J.Kim, T.M.Logan, and M.Blaber (2003).
Accommodation of a highly symmetric core within a symmetric protein superfold.
  Protein Sci, 12, 2704-2718.
PDB codes: 1jy0 1m16 1nzk 1p63
11880654 F.J.Miana-Mena, S.Roux, J.C.Benichou, R.Osta, and P.Brûlet (2002).
Neuronal activity-dependent membrane traffic at the neuromuscular junction.
  Proc Natl Acad Sci U S A, 99, 3234-3239.  
12417130 K.Turton, J.A.Chaddock, and K.R.Acharya (2002).
Botulinum and tetanus neurotoxins: structure, function and therapeutic utility.
  Trends Biochem Sci, 27, 552-558.  
  11598183 J.Herreros, T.Ng, and G.Schiavo (2001).
Lipid rafts act as specialized domains for tetanus toxin binding and internalization into neurons.
  Mol Biol Cell, 12, 2947-2960.  
11714927 S.R.Brych, S.I.Blaber, T.M.Logan, and M.Blaber (2001).
Structure and stability effects of mutations designed to increase the primary sequence symmetry within the core region of a beta-trefoil.
  Protein Sci, 10, 2587-2599.
PDB codes: 1jqz 1jt3 1jt4 1jt5 1jt7 1jtc
10795737 A.N.Antoniou, S.L.Blackwood, D.Mazzeo, and C.Watts (2000).
Control of antigen presentation by a single protease cleavage site.
  Immunity, 12, 391-398.  
10972823 K.Sinha, M.Box, G.Lalli, G.Schiavo, H.Schneider, M.Groves, G.Siligardi, and N.Fairweather (2000).
Analysis of mutants of tetanus toxin Hc fragment: ganglioside binding, cell binding and retrograde axonal transport properties.
  Mol Microbiol, 37, 1041-1051.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.

 

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