Sandbox Reserved 492: Difference between revisions
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== Cholix Toxin from ''Vibrio Cholerae ''== | == Cholix Toxin from ''Vibrio Cholerae ''== | ||
The [http://en.wikipedia.org/wiki/Crystal_structure crystal structure] of the purified form of ''' Cholix Toxin''' or '''CT''' was determined in 1995. [3] It is an oligomeric bacterial protein found to be made up of six individual <scene name='Sandbox_Reserved_496/Secondary_structure/1'>subunits, </scene> one single α-subunit and 5 individual β- subunits.The α-subunit makes up what is known as the enzymatic portion of the protein while the 5 copies of the β-subunit are responsible for the binding to the ligand receptor. The toxin binds highly specifically and tightly to a [http://en.wikipedia.org/wiki/GM1_gangliosidoses GM1 gangliosides] on the surface of the host's cells. In this X-Ray Diffraction image we can see the <scene name='Sandbox_Reserved_496/Binding_site/1'>catalytic</scene> site, which in this case has been complexed with an allosteric inhibitor (red and yellow space filling atoms). Recent studies have indicated several amino acid <scene name='Sandbox_Reserved_496/Critical_amino_acids/2'> residues </scene> located proximally to the active site which are critical for enzymatic activity. Specifically, site directed mutagenesis indicated that when altered, the mutation results in a termination of the proteins toxicity, rendering it essentially harmless. | The [http://en.wikipedia.org/wiki/Crystal_structure crystal structure] of the purified form of ''' Cholix Toxin''' or '''CT''' was determined in 1995. [3] It is an oligomeric bacterial protein found to be made up of six individual <scene name='Sandbox_Reserved_496/Secondary_structure/1'>subunits, </scene> one single α-subunit and 5 individual β- subunits.The α-subunit makes up what is known as the enzymatic portion of the protein while the 5 copies of the β-subunit are responsible for the binding to the ligand receptor. The toxin binds highly specifically and tightly to a [http://en.wikipedia.org/wiki/GM1_gangliosidoses GM1 gangliosides] on the surface of the host's cells. In this X-Ray Diffraction image we can see the <scene name='Sandbox_Reserved_496/Binding_site/1'>catalytic</scene> site, which in this case has been complexed with an allosteric inhibitor (red and yellow space filling atoms). Recent studies have indicated several amino acid <scene name='Sandbox_Reserved_496/Critical_amino_acids/2'> residues </scene> located proximally to the active site which are critical for enzymatic activity. Specifically, site directed mutagenesis indicated that when altered, the mutation results in a termination of the proteins toxicity, rendering it essentially harmless. | ||
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== '''Toxin Mechanism''' == | == '''Toxin Mechanism''' == | ||
Once secreted, the B subunit will bind to GM1 gangliosides on the surface. After binding takes place, the whole complex is engulfed by the cell and a portion known as the CTA1 chain is detached after reduction of a disulfide bridge. The new endosome is moved to the Golgi, where it is recognized by the endoplasmic reticulum, unfolded and delivered to the membrane, where the Endoplasmic Reticulum-oxidase - "'''Ero1'''" triggers the release of the excised A1 protein (through Oxidation) of '''protein disulfide isomerase complex'''. As A1 moves from the ER into the cytoplasm it refolds and avoids further reduction.[1] | Once secreted, the B subunit will bind to GM1 gangliosides on the surface. After ''binding'' takes place, the whole complex is engulfed by the cell and a portion known as the CTA1 chain is detached after reduction of a disulfide bridge. The new endosome is moved to the Golgi, where it is recognized by the endoplasmic reticulum, unfolded and delivered to the membrane, where the Endoplasmic Reticulum-oxidase - "'''Ero1'''" triggers the release of the excised A1 protein (through Oxidation) of '''protein disulfide isomerase complex'''. As A1 moves from the ER into the cytoplasm it refolds and avoids further reduction.[1] | ||
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== '''Uses & Potential Benefits''' == | == '''Uses & Potential Benefits''' == | ||
=An aspiration for research being done on the Cholera Toxin coincides with a current "hot topic" within the science community and society around the world: '''Stem Cell Research.''' There have been some recent findings indicating that the protein may be capable of interacting - regulation on the genetic level - some key factors in Neural Stem Cell '''(NSC)''' regeneration and differentiation. Known as Tie2, a membrane receptor, and Hes3 a transcription factor, these two indicators have been shown to directly interact with the Cholix Toxin. Moreover, there are even some implications that the protein, when combined with specific medium, boosted Stem Cell culture growth.[5] Thus, we see that apart from its potential to cause human illness, CX also poses the potential to offer a solution to cancer and other related diseases. | |||