1lt3
From Proteopedia
(New page: 200px<br /><applet load="1lt3" size="450" color="white" frame="true" align="right" spinBox="true" caption="1lt3, resolution 2.0Å" /> '''HEAT-LABILE ENTEROTOX...) |
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| - | [[Image:1lt3.jpg|left|200px]]<br /><applet load="1lt3" size=" | + | [[Image:1lt3.jpg|left|200px]]<br /><applet load="1lt3" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1lt3, resolution 2.0Å" /> | caption="1lt3, resolution 2.0Å" /> | ||
'''HEAT-LABILE ENTEROTOXIN DOUBLE MUTANT N40C/G166C'''<br /> | '''HEAT-LABILE ENTEROTOXIN DOUBLE MUTANT N40C/G166C'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Cholera toxin (CT) produced by Vibrio cholerae and heat-labile enterotoxin | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1LT3 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http:// | + | 1LT3 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LT3 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Escherichia coli]] | [[Category: Escherichia coli]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Akker, F | + | [[Category: Akker, F Van Den.]] |
| - | [[Category: Hol, W | + | [[Category: Hol, W G.J.]] |
[[Category: enterotoxin]] | [[Category: enterotoxin]] | ||
[[Category: signal]] | [[Category: signal]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:48:12 2008'' |
Revision as of 11:48, 21 February 2008
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HEAT-LABILE ENTEROTOXIN DOUBLE MUTANT N40C/G166C
Overview
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.
About this Structure
1LT3 is a Protein complex structure of sequences from Escherichia coli. Full crystallographic information is available from OCA.
Reference
Crystal structure of heat-labile enterotoxin from Escherichia coli with increased thermostability introduced by an engineered disulfide bond in the A subunit., van den Akker F, Feil IK, Roach C, Platas AA, Merritt EA, Hol WG, Protein Sci. 1997 Dec;6(12):2644-9. PMID:9416616
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