Sandbox Reserved 466: Difference between revisions

From Proteopedia
Jump to navigationJump to search
← Older editNewer edit →
No edit summary
No edit summary
Line 21: Line 21:


Tetanus toxin has three functional domains: binding, translocation, and catalytic. The heavy chain is responsible for binding the toxin to the presynaptic neuron membrane and translocating the catalytic light chain domain into the neural cytosol. The light chain is the zinc-dependent catalytic domain containing a zinc-binding motif. This metalloprotease activity causes toxicity [Rao et al., 2005]. The light chain forms a dimer with about 10% of the protein surface existing between the two monomers. Each monomer binds one <scene name='Sandbox_Reserved_466/Zinc_ion/1'>zinc ion</scene>. The active sites of the light chain tetanus toxin interact with the solvent region and are embedded inside a cavity centered around a zinc cation and the conserved zinc-dependent motif. Zinc directly coordinates with His232, His236, and Glu271 within the zinc-dependent <scene name='Sandbox_Reserved_466/Active_site/1'>active site</scene>. Water is another ligand that forms a hydrogen bond with Glu233. The formation of the nucleophilic water molecule and the three other amino acid residues in the [http://ars.els-cdn.com/content/image/1-s2.0-S004101010000252X-gr1.jpg tetanus toxin active site] [Rossetto et al., 2001] form a tetrahedral configuration around the catalytic zinc ion. There is also a secondary layer important to the functionality of the active site. These residues are in the surrounding structure, approximately 10 Angstroms from the zinc ion, and they include Glu233, His239, Phe274, Arg371, and Tyr374. These residues reinforce the stability and conformation of the active site [Rao et al., 2005].  
Tetanus toxin has three functional domains: binding, translocation, and catalytic. The heavy chain is responsible for binding the toxin to the presynaptic neuron membrane and translocating the catalytic light chain domain into the neural cytosol. The light chain is the zinc-dependent catalytic domain containing a zinc-binding motif. This metalloprotease activity causes toxicity [Rao et al., 2005]. The light chain forms a dimer with about 10% of the protein surface existing between the two monomers. Each monomer binds one <scene name='Sandbox_Reserved_466/Zinc_ion/1'>zinc ion</scene>. The active sites of the light chain tetanus toxin interact with the solvent region and are embedded inside a cavity centered around a zinc cation and the conserved zinc-dependent motif. Zinc directly coordinates with His232, His236, and Glu271 within the zinc-dependent <scene name='Sandbox_Reserved_466/Active_site/1'>active site</scene>. Water is another ligand that forms a hydrogen bond with Glu233. The formation of the nucleophilic water molecule and the three other amino acid residues in the [http://ars.els-cdn.com/content/image/1-s2.0-S004101010000252X-gr1.jpg tetanus toxin active site] [Rossetto et al., 2001] form a tetrahedral configuration around the catalytic zinc ion. There is also a secondary layer important to the functionality of the active site. These residues are in the surrounding structure, approximately 10 Angstroms from the zinc ion, and they include Glu233, His239, Phe274, Arg371, and Tyr374. These residues reinforce the stability and conformation of the active site [Rao et al., 2005].  
The structure of the tetanus toxin was determined by various methods, such as X-ray crystallography, ultraviolet and atomic absorption spectroscopy, fluorescence spectroscopy, and circular dichromism spectroscopy [Rao et al., 2005 and Rossetto et al., 2001].




Line 31: Line 34:
This interaction between the residues, water, and zinc are essential for the formation of nucleophilic water, which hydrolyzes the peptide bonds of the substrate. The three amino acids His232, His236, and Glu271 directly coordinate with the zinc ion. A water molecule, which is the fourth ligand, forms a strong hydrogen bond with another glutamate residue (Glu233) that is part of the secondary surrounding active residues. The delta-carbonyl of Glu233 orients the nucleophilic water molecule into a tetrahedral formation around the [http://ars.els-cdn.com/content/image/1-s2.0-S0041010105000929-gr1.jpg catalytic zinc ion] [Rao et al., 2005]. This formation around the zinc is essential to the formation of the nucleophilic water, which hydrolyzes the peptide bond Gln76-Phe77 of the synaptobrevin VAMP protein.  
This interaction between the residues, water, and zinc are essential for the formation of nucleophilic water, which hydrolyzes the peptide bonds of the substrate. The three amino acids His232, His236, and Glu271 directly coordinate with the zinc ion. A water molecule, which is the fourth ligand, forms a strong hydrogen bond with another glutamate residue (Glu233) that is part of the secondary surrounding active residues. The delta-carbonyl of Glu233 orients the nucleophilic water molecule into a tetrahedral formation around the [http://ars.els-cdn.com/content/image/1-s2.0-S0041010105000929-gr1.jpg catalytic zinc ion] [Rao et al., 2005]. This formation around the zinc is essential to the formation of the nucleophilic water, which hydrolyzes the peptide bond Gln76-Phe77 of the synaptobrevin VAMP protein.  


The structure of the tetanus toxin was determined by various methods, such as X-ray crystallography,




Retrieved from "https://proteopedia.org/Sandbox_Reserved_466"