 |
PDBsum entry 1fv3
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
The crystal structure of tetanus toxin hc fragment complexed with a synthetic gt1b analogue suggests cross-Linking between ganglioside receptors and the toxin.
|
|
|
Authors
|
|
C.Fotinou,
P.Emsley,
I.Black,
H.Ando,
H.Ishida,
M.Kiso,
K.A.Sinha,
N.F.Fairweather,
N.W.Isaacs.
|
|
|
Ref.
|
|
J Biol Chem, 2001,
276,
32274-32281.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
|
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.
|
|
|
Secondary reference #1
|
|
|
Title
|
|
The structures of the h(c) fragment of tetanus toxin with carbohydrate subunit complexes provide insight into ganglioside binding.
|
|
|
Authors
|
|
P.Emsley,
C.Fotinou,
I.Black,
N.F.Fairweather,
I.G.Charles,
C.Watts,
E.Hewitt,
N.W.Isaacs.
|
|
|
Ref.
|
|
J Biol Chem, 2000,
275,
8889-8894.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
|
|
|
|
|
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
reproduced from the cited reference
with permission from the ASBMB
|
|
|
Secondary reference #2
|
|
|
Title
|
|
Structure of the receptor binding fragment hc of tetanus neurotoxin.
|
|
|
Authors
|
|
T.C.Umland,
L.M.Wingert,
S.Swaminathan,
W.F.Furey,
J.J.Schmidt,
M.Sax.
|
|
|
Ref.
|
|
Nat Struct Biol, 1997,
4,
788-792.
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
|
|
|
|
