Common binding site for disialyllactose and tri-peptide in C-fragment of tetanus neurotoxin

Proteins. 2005 Nov 1;61(2):288-95. doi: 10.1002/prot.20595.


Clostridial neurotoxins are comprised of botulinum (BoNT) and tetanus (TeNT), which share significant structural and functional similarity. Crystal structures of the binding domain of TeNT complexed with disialyllactose (DiSia) and a tri-peptide Tyr-Glu-Trp (YEW) have been determined to 2.3 and 2.2 A, respectively. Both DiSia and YEW bind in a shallow cleft region on the surface of the molecule in the beta-trefoil domain, interacting with a set of common residues, Asp1147, Asp1214, Asn1216, and Arg1226. DiSia and YEW binding at the same site in tetanus toxin provides a putative site that could be occupied either by a ganglioside moiety or a peptide. Soaking experiments with a mixture of YEW and DiSia show that YEW competes with DiSia, suggesting that YEW can be used to block ganglioside binding. A comparison with the TeNT binding domain in complex with small molecules, BoNT/A and /B, provides insight into the different modes of ganglioside binding.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Botulinum Toxins / chemistry
  • Botulinum Toxins, Type A / chemistry
  • Crystallography, X-Ray
  • Gangliosides / chemistry
  • Metalloendopeptidases / chemistry*
  • Models, Molecular
  • Molecular Sequence Data
  • Oligopeptides / chemistry*
  • Protein Structure, Tertiary
  • Sequence Alignment
  • Structural Homology, Protein
  • Tetanus Toxin / chemistry*
  • Trisaccharides / chemistry*


  • Gangliosides
  • Oligopeptides
  • Tetanus Toxin
  • Trisaccharides
  • disialyllactose
  • tyrosyl-glutamyl-tryptophan
  • rimabotulinumtoxinB
  • tetanospasmin
  • trisialoganglioside GT1
  • Metalloendopeptidases
  • Botulinum Toxins
  • Botulinum Toxins, Type A