|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
12
|
|
pubmed:dateCreated |
1998-2-10
|
|
pubmed:abstractText |
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.
|
|
pubmed:grant |
|
|
pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/9416616-1238506,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9416616-1304882,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9416616-15299354,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9416616-1741035,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9416616-17810339,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9416616-1784181,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9416616-2034287,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9416616-221485,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9416616-2334683,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9416616-3081893,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9416616-3096989,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9416616-3214,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9416616-3244694,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9416616-3378043,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9416616-6233359,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9416616-6273411,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9416616-7490296,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9416616-7502872,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9416616-7537085,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9416616-7658473,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9416616-7669757,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9416616-7729864,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9416616-7878032,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9416616-7898381,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9416616-8132565,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9416616-8478941,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9416616-8718582,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9416616-8793878,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9416616-8861953,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9416616-8945598
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Dec
|
|
pubmed:issn |
0961-8368
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:volume |
6
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
2644-9
|
|
pubmed:dateRevised |
2010-9-13
|
|
pubmed:meshHeading |
pubmed-meshheading:9416616-Bacterial Toxins,
pubmed-meshheading:9416616-Bacterial Vaccines,
pubmed-meshheading:9416616-Crystallization,
pubmed-meshheading:9416616-Crystallography, X-Ray,
pubmed-meshheading:9416616-Disulfides,
pubmed-meshheading:9416616-Drug Stability,
pubmed-meshheading:9416616-Enterotoxins,
pubmed-meshheading:9416616-Escherichia coli,
pubmed-meshheading:9416616-Escherichia coli Proteins,
pubmed-meshheading:9416616-Hot Temperature,
pubmed-meshheading:9416616-Models, Molecular,
pubmed-meshheading:9416616-Molecular Structure,
pubmed-meshheading:9416616-Mutagenesis,
pubmed-meshheading:9416616-Protein Engineering
|
|
pubmed:year |
1997
|
|
pubmed:articleTitle |
Crystal structure of heat-labile enterotoxin from Escherichia coli with increased thermostability introduced by an engineered disulfide bond in the A subunit.
|
|
pubmed:affiliation |
Department of Biochemistry, University of Washington, Seattle 98195-7420, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|
