1lt4
From Proteopedia
(New page: 200px<br /><applet load="1lt4" size="450" color="white" frame="true" align="right" spinBox="true" caption="1lt4, resolution 2.0Å" /> '''HEAT-LABILE ENTEROTOX...) |
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| - | [[Image:1lt4.gif|left|200px]]<br /><applet load="1lt4" size=" | + | [[Image:1lt4.gif|left|200px]]<br /><applet load="1lt4" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1lt4, resolution 2.0Å" /> | caption="1lt4, resolution 2.0Å" /> | ||
'''HEAT-LABILE ENTEROTOXIN MUTANT S63K'''<br /> | '''HEAT-LABILE ENTEROTOXIN MUTANT S63K'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Two closely related bacterial toxins, heat-labile enterotoxin (LT-I) and | + | Two closely related bacterial toxins, heat-labile enterotoxin (LT-I) and cholera toxin (CT), not only invoke a toxic activity that affects many victims worldwide but also contain a beneficial mucosal adjuvant activity that significantly enhances the potency of vaccines in general. For the purpose of vaccine design it is most interesting that the undesirable toxic activity of these toxins can be eliminated by the single-site mutation Ser63Lys in the A subunit while the mucosal adjuvant activity is still present. The crystal structure of the Ser63Lys mutant of LT-I is determined at 2.0 A resolution. Its structure appears to be essentially the same as the wild-type LT-I structure. The substitution Ser63Lys was designed, based on the wild-type LT-I crystal structure, to decrease toxicity by interfering with NAD binding and/or catalysis. In the mutant crystal structure, the newly introduced lysine side chain is indeed positioned such that it could potentially obstruct the productive binding mode of the substrate NAD while at the same time its positive charge could possibly interfere with the critical function of nearby charged groups in the active site of LT-I. The fact that the Ser63Lys mutant of LT-I does not disrupt the wild-type LT-I structure makes the non-toxic mutant potentially suitable, from a structural point of view, to be used as a vaccine to prevent enterotoxigenic E. coli infections. The structural similarity of mutant and wild-type toxin might also be the reason why the inactive Ser63Lys variant retains its adjuvant activity. |
==About this Structure== | ==About this Structure== | ||
| - | 1LT4 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:// | + | 1LT4 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=1LT4 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]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:48:11 2008'' |
Revision as of 11:48, 21 February 2008
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HEAT-LABILE ENTEROTOXIN MUTANT S63K
Overview
Two closely related bacterial toxins, heat-labile enterotoxin (LT-I) and cholera toxin (CT), not only invoke a toxic activity that affects many victims worldwide but also contain a beneficial mucosal adjuvant activity that significantly enhances the potency of vaccines in general. For the purpose of vaccine design it is most interesting that the undesirable toxic activity of these toxins can be eliminated by the single-site mutation Ser63Lys in the A subunit while the mucosal adjuvant activity is still present. The crystal structure of the Ser63Lys mutant of LT-I is determined at 2.0 A resolution. Its structure appears to be essentially the same as the wild-type LT-I structure. The substitution Ser63Lys was designed, based on the wild-type LT-I crystal structure, to decrease toxicity by interfering with NAD binding and/or catalysis. In the mutant crystal structure, the newly introduced lysine side chain is indeed positioned such that it could potentially obstruct the productive binding mode of the substrate NAD while at the same time its positive charge could possibly interfere with the critical function of nearby charged groups in the active site of LT-I. The fact that the Ser63Lys mutant of LT-I does not disrupt the wild-type LT-I structure makes the non-toxic mutant potentially suitable, from a structural point of view, to be used as a vaccine to prevent enterotoxigenic E. coli infections. The structural similarity of mutant and wild-type toxin might also be the reason why the inactive Ser63Lys variant retains its adjuvant activity.
About this Structure
1LT4 is a Protein complex structure of sequences from Escherichia coli. Full crystallographic information is available from OCA.
Reference
Crystal structure of a non-toxic mutant of heat-labile enterotoxin, which is a potent mucosal adjuvant., van den Akker F, Pizza M, Rappuoli R, Hol WG, Protein Sci. 1997 Dec;6(12):2650-4. PMID:9416617
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