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Common binding site for disialyllactose and tri‐peptide in C‐fragment of tetanus neurotoxin
Author(s) -
Jayaraman Seetharaman,
Eswaramoorthy Subramaniam,
Kumaran Desigan,
Swaminathan Subramanyam
Publication year - 2005
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.20595
Subject(s) - ganglioside , peptide , binding site , toxin , stereochemistry , moiety , chemistry , neurotoxin , structural similarity , biochemistry , biology
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 Å, respectively. Both DiSia and YEW bind in a shallow cleft region on the surface of the molecule in the β‐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. Proteins 2005. Published 2005 Wiley‐Liss, Inc.