Sandbox Reserved 486: Difference between revisions

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== Mechanism ==

The mechanism begins by the R domain recognizing the target cells by the molecules on the cells surface. A prominent β-hairpin loop of the R domain binds to the surface and allows for a docking station. Binding leads to receptor mediated endocytosis. The T domain translocates the C domain into the cytosol of the cell. The organism ''Corynebacterium diphtheriae'' first secretes the toxin the loop between the C and T domain has to be nicked in order for the toxicity to be turned on. There is one surface protease named [http://en.wikipedia.org/wiki/Furin furin] that is known to nick the area but it is unclear if any other protein helps the process. This process allows for the C domain to dissociate from the T domain after transported(translocated) into the cytosol. This is where the disulfide bonds become reduced.

The mechanism begins by the R domain recognizing the target cells by the molecules on the cells surface. A prominent β-hairpin loop of the R domain binds to the surface and allows for a docking station. Binding leads to receptor mediated endocytosis. The T domain translocates the C domain into the cytosol of the cell. The organism ''Corynebacterium diphtheriae'' first secretes the toxin the loop between the C and T domain has to be nicked in order for the toxicity to be turned on. There is one surface protease named [http://en.wikipedia.org/wiki/Furin furin] that is known to nick the area but it is unclear if any other protein helps the process. This process allows for the C domain to dissociate from the T domain after transported(translocated) into the cytosol. This is where the disulfide bonds become reduced. After this happens a drop in pH leads to the formation of the dimer to become an open monomer form. The reduction of the disulfide bonds is the rate determining step of the toxin entrying the cell.

Once entried into the cytosol, the C domain does ADP-ribosylation of EF-2 at diphthamide, a posttranslationally modified histidine residue. This shuts down all protein synthesis and kills the cell. The Kcat/KM of the reaction is about 108 min-1 M-1. The figure below shows the reaction happening at the C domain.

Sandbox Reserved 486: Difference between revisions

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 == Mechanism ==
-The mechanism begins by the R domain recognizing the target cells by the molecules on the cells surface. A prominent β-hairpin loop of the R domain binds to the surface and allows for a docking station. Binding leads to receptor mediated endocytosis. The T domain translocates the C domain into the cytosol of the cell. The organism ''Corynebacterium diphtheriae'' first secretes the toxin the loop between the C and T domain has to be nicked in order for the toxicity to be turned on. There is one surface protease named [http://en.wikipedia.org/wiki/Furin furin] that is known to nick the area but it is unclear if any other protein helps the process. This process allows for the C domain to dissociate from the T domain after transported(translocated) into the cytosol. This is where the disulfide bonds become reduced.
+The mechanism begins by the R domain recognizing the target cells by the molecules on the cells surface. A prominent β-hairpin loop of the R domain binds to the surface and allows for a docking station. Binding leads to receptor mediated endocytosis. The T domain translocates the C domain into the cytosol of the cell. The organism ''Corynebacterium diphtheriae'' first secretes the toxin the loop between the C and T domain has to be nicked in order for the toxicity to be turned on. There is one surface protease named [http://en.wikipedia.org/wiki/Furin furin] that is known to nick the area but it is unclear if any other protein helps the process. This process allows for the C domain to dissociate from the T domain after transported(translocated) into the cytosol. This is where the disulfide bonds become reduced. After this happens a drop in pH leads to the formation of the dimer to become an open monomer form. The reduction of the disulfide bonds is the rate determining step of the toxin entrying the cell.
+Once entried into the cytosol, the C domain does ADP-ribosylation of EF-2 at diphthamide, a posttranslationally modified histidine residue.  This shuts down all protein synthesis and kills the cell. The K<sub>cat</sub>/K<sub>M</sub> of the reaction is about 10<sup>8</sup> min<sup>-1</sup> M<sup>-1</sup>. The figure below shows the reaction happening at the C domain.