Sandbox Reserved 702: Difference between revisions
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*'''Lethal factor (LF)''' | *'''Lethal factor (LF)''' | ||
LF is a zinc-mediated metalloprotease that cleaves mitogen-activated protein kinase kinases (MEKs). This impairs cell signaling, and results in the induction of apoptosis. <ref>Klimpel, K. R., N. Arora, and S. H. Leppla. 1994. Anthrax toxin lethal factor contains a zinc metalloprotease consensus sequence which is required for lethal toxin activity. Mol. Microbiol. 13:1093–1100</ref> | LF is a zinc-mediated metalloprotease that cleaves mitogen-activated protein kinase kinases (MEKs). This impairs cell signaling, and results in the induction of apoptosis. <ref>Klimpel, K. R., N. Arora, and S. H. Leppla. 1994. Anthrax toxin lethal factor contains a zinc metalloprotease consensus sequence which is required for lethal toxin activity. Mol. Microbiol. 13:1093–1100</ref> | ||
*'''Edema factor (EF)''' | *'''Edema factor (EF)''' | ||
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The edema factor is delivered into host cells thanks to the protective antigen. Indeed, the protective antigen binds to cellular receptors (CMP2, capillary morphogenesis protein 2 or TEM8, tumor endothelial marker 8) and is cleaved at the sequence arginine-lysine-lysine-arginine by cell surface proteases. This '''proteolytic activation''' leads to the oligomerisation of a '''protective antigen heptamer'''. The heptamer is composed of the <scene name='Sandbox_Reserved_702/Coloration_from_n_to_c_term/1'>C-terminal</scene> 63 kDa fragment. One heptamer can bind three molecules of edema factor (or lethal factor). Such a complex gets into the cell by endocytosis and finally the protective antigen helps the translocation of the edema factor from late endosome into the cytoplasm. Once it is in the host cell, the '''edema factor becomes membrane-associated'''. ''It is not known whether it is due to its association with [[calmodulin]] or to its binding with other cellular elements''. <ref> PMID: 19560485</ref> | The edema factor is delivered into host cells thanks to the protective antigen. Indeed, the protective antigen binds to cellular receptors (CMP2, capillary morphogenesis protein 2 or TEM8, tumor endothelial marker 8) and is cleaved at the sequence arginine-lysine-lysine-arginine by cell surface proteases. This '''proteolytic activation''' leads to the oligomerisation of a '''protective antigen heptamer'''. The heptamer is composed of the <scene name='Sandbox_Reserved_702/Coloration_from_n_to_c_term/1'>C-terminal</scene> 63 kDa fragment. One heptamer can bind three molecules of edema factor (or lethal factor). Such a complex gets into the cell by endocytosis and finally the protective antigen helps the translocation of the edema factor from late endosome into the cytoplasm. Once it is in the host cell, the '''edema factor becomes membrane-associated'''. ''It is not known whether it is due to its association with [[calmodulin]] or to its binding with other cellular elements''. <ref> PMID: 19560485</ref> | ||
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{{Template:ColorKey Composition Ligand}} | {{Template:ColorKey Composition Ligand}} | ||
{{Template:ColorKey Composition Solvent}} | {{Template:ColorKey Composition Solvent}} | ||
The '''helical domain of the edema factor''' interacts with the [[adenylate cyclase]] domain and '''switch C''' in the '''absence of [[calmodulin]]'''. This locks the enzyme in an '''inactive''' state. | The '''helical domain of the edema factor''' interacts with the [[adenylate cyclase]] domain and '''switch C''' in the '''absence of [[calmodulin]]'''. This locks the enzyme in an '''inactive''' state. | ||
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<scene name='Sandbox_Reserved_702/Histidine_351/1'>Histidine 351</scene> also plays a key role in the [[adenylyl cyclase]] reaction. Histidine is a crucial amino acid because its pKa (6.8) is close to pH of cytoplasm. | <scene name='Sandbox_Reserved_702/Histidine_351/1'>Histidine 351</scene> also plays a key role in the [[adenylyl cyclase]] reaction. Histidine is a crucial amino acid because its pKa (6.8) is close to pH of cytoplasm. | ||
It may intervene in proton-transfer reactions. Histidine 351 has a critical role in the catalytic activity of edema factor but is not a catalytic base. Since it is about 6.0 Å away from the 3'O of cAMP, its role is to allow a water molecule to enter between them. Histidine does not act as a general base (acceptor of 3'OH proton), but is facilitates an increase in the concentration of HO- ions in the proximity of the 3'OH group. <ref> PMID: 15719022</ref> | It may intervene in proton-transfer reactions. Histidine 351 has a critical role in the catalytic activity of edema factor but is not a catalytic base. Since it is about 6.0 Å away from the 3'O of cAMP, its role is to allow a water molecule to enter between them. Histidine does not act as a general base (acceptor of 3'OH proton), but is facilitates an increase in the concentration of HO- ions in the proximity of the 3'OH group. <ref> PMID: 15719022</ref> | ||
