PDBsum entry 1fv3

Toxin

PDB id: 1fv3

Contents

Protein chains

451 a.a. *

Ligands

BGC-GAL-NGA-GAL-SIA-SLB-SIA ×2

CEQ ×2

PO4

Waters ×241

* Residue conservation analysis

PDB id:

1fv3

Name:

Toxin

Title:

The hc fragment of tetanus toxin complexed with an analogue of its ganglioside receptor gt1b

Structure:

Tetanus toxin heavy chain. Chain: a, b. Fragment: c-terminal domain of heavy chain. Engineered: yes

Source:

Clostridium tetani. Organism_taxid: 1513. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.30Å R-factor: 0.239 R-free: 0.306

Authors:

C.Fotinou,P.Emsley,I.Black,H.Ando,H.Ishida,M.Kiso,K.A.Sinha, N.F.Fairweather,N.W.Isaacs

Key ref:

C.Fotinou et al. (2001). The crystal structure of tetanus toxin Hc fragment complexed with a synthetic GT1b analogue suggests cross-linking between ganglioside receptors and the toxin. J Biol Chem, 276, 32274-32281. PubMed id: 11418600 DOI: 10.1074/jbc.M103285200

Date:

18-Sep-00 Release date: 05-Sep-01

Protein chains

P04958  (TETX_CLOTE) -  Tetanus toxin from Clostridium tetani (strain Massachusetts / E88)

Seq: 1315 a.a.

Struc: 451 a.a.

Enzyme reactions

• Enzyme class: E.C.3.4.24.68 - tentoxilysin.
• Reaction: Hydrolysis of 76-Gln-|-Phe-77 bond in synaptobrevin 2.
• Cofactor: Zn(2+)

DOI no: 10.1074/jbc.M103285200

J Biol Chem 276:32274-32281 (2001)

PubMed id: 11418600

The crystal structure of tetanus toxin Hc fragment complexed with a synthetic GT1b analogue suggests cross-linking between ganglioside receptors and the toxin.

C.Fotinou, P.Emsley, I.Black, H.Ando, H.Ishida, M.Kiso, K.A.Sinha, N.F.Fairweather, N.W.Isaacs.

ABSTRACT

Tetanus toxin, a member of the family of Clostridial neurotoxins, is one of the most potent toxins known. The crystal structure of the complex of the COOH-terminal fragment of the heavy chain with an analogue of its ganglioside receptor, GT1b, provides the first direct identification and characterization of the ganglioside-binding sites. The ganglioside induces cross-linking by binding to two distinct sites on the Hc molecule. The structure sheds new light on the binding of Clostridial neurotoxins to receptors on neuronal cells and provides important information relevant to the design of anti-tetanus and anti-botulism therapeutic agents.

Selected figure(s)

Figure 5.
Fig. 5. Stereo view of the surfaces of the two binding sites of H[C] with the interacting ganglioside. The Gal4-GalNAc3 site is a deep cleft on one H[C] (red) and the Sia7-Sia6 a shallow groove on the other (blue). The protein residues forming the binding sites are shown.

Figure 6.
Fig. 6. Stereo view of the ganglioside-protein binding sites. a, the Gal4-GalNAc3 site is a groove formed by Trp1289, His1271, and Tyr1290. The hydrophobic face of Gal4 packs against the indole ring of Trp1289. This packing is extended through His1293, Phe^1218, and His1271. Hydrogen bonds are shown as dotted lines. b, the Sia7-Sia6 site consists of residues Asp1147, Arg1226, Asn1216, Asp1214, and Tyr1229. The disialo group binds to the protein through hydrogen bonds that are shown as dotted lines.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2001, 276, 32274-32281) copyright 2001.

Figures were selected by the author.