 |
PDBsum entry 1lt3
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Crystal structure of heat-Labile enterotoxin from escherichia coli with increased thermostability introduced by an engineered disulfide bond in the a subunit.
|
|
|
Authors
|
|
F.Van den akker,
I.K.Feil,
C.Roach,
A.A.Platas,
E.A.Merritt,
W.G.Hol.
|
|
|
Ref.
|
|
Protein Sci, 1997,
6,
2644-2649.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
percentage match of
97%.
|
|
|
|
Abstract
|
|
|
Cholera toxin (CT) produced by Vibrio cholerae and heat-labile enterotoxin
(LT-I), produced by enterotoxigenic Escherichia coli, are AB5 heterohexamers
with an ADP-ribosylating A subunit and a GM1 receptor binding B pentamer. These
toxins are among the most potent mucosal adjuvants known and, hence, are of
interest both for the development of anti-diarrheal vaccines against cholera or
enterotoxigenic Escherichia coli diarrhea and also for vaccines in general.
However, the A subunits of CT and LT-I are known to be relatively temperature
sensitive. To improve the thermostability of LT-I an additional disulfide bond
was introduced in the A1 subunit by means of the double mutation N40C and G166C.
The crystal structure of this double mutant of LT-I has been determined to 2.0 A
resolution. The protein structure of the N40C/G166C double mutant is very
similar to the native structure except for a few local shifts near the new
disulfide bond. The introduction of this additional disulfide bond increases the
thermal stability of the A subunit of LT-I by 6 degrees C. The enhancement in
thermostability could make this disulfide bond variant of LT-I of considerable
interest for the design of enterotoxin-based vaccines.
|
|
|
Secondary reference #1
|
|
|
Title
|
|
Refined structure of escherichia coli heat-Labile enterotoxin, A close relative of cholera toxin.
|
|
|
Authors
|
|
T.K.Sixma,
K.H.Kalk,
B.A.Van zanten,
Z.Dauter,
J.Kingma,
B.Witholt,
W.G.Hol.
|
|
|
Ref.
|
|
J Mol Biol, 1993,
230,
890-918.
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
Secondary reference #2
|
|
|
Title
|
|
Crystal structure of a cholera toxin-Related heat-Labile enterotoxin from e. Coli.
|
|
|
Authors
|
|
T.K.Sixma,
S.E.Pronk,
K.H.Kalk,
E.S.Wartna,
B.A.Van zanten,
B.Witholt,
W.G.Hol.
|
|
|
Ref.
|
|
Nature, 1991,
351,
371-377.
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
|
|
|
|
