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PDBsum entry 1lt3
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* Residue conservation analysis
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DOI no:
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Protein Sci
6:2644-2649
(1997)
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PubMed id:
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Crystal structure of heat-labile enterotoxin from Escherichia coli with increased thermostability introduced by an engineered disulfide bond in the A subunit.
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F.van den Akker,
I.K.Feil,
C.Roach,
A.A.Platas,
E.A.Merritt,
W.G.Hol.
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ABSTRACT
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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.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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J.L.Pellequer,
and
S.W.Chen
(2006).
Multi-template approach to modeling engineered disulfide bonds.
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Proteins,
65,
192-202.
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O.R.Siadat,
A.Lougarre,
L.Lamouroux,
C.Ladurantie,
and
D.Fournier
(2006).
The effect of engineered disulfide bonds on the stability of Drosophila melanogaster acetylcholinesterase.
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BMC Biochem,
7,
12.
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R.Schultz-Heienbrok,
T.Maier,
and
N.Sträter
(2004).
Trapping a 96 degrees domain rotation in two distinct conformations by engineered disulfide bridges.
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Protein Sci,
13,
1811-1822.
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PDB codes:
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H.Ogino,
T.Uchiho,
J.Yokoo,
R.Kobayashi,
R.Ichise,
and
H.Ishikawa
(2001).
Role of intermolecular disulfide bonds of the organic solvent-stable PST-01 protease in its organic solvent stability.
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Appl Environ Microbiol,
67,
942-947.
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R.E.Burton,
J.A.Hunt,
C.A.Fierke,
and
T.G.Oas
(2000).
Novel disulfide engineering in human carbonic anhydrase II using the PAIRWISE side-chain geometry database.
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Protein Sci,
9,
776-785.
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K.Gruber,
G.Klintschar,
M.Hayn,
A.Schlacher,
W.Steiner,
and
C.Kratky
(1998).
Thermophilic xylanase from Thermomyces lanuginosus: high-resolution X-ray structure and modeling studies.
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Biochemistry,
37,
13475-13485.
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PDB code:
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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Links
