Sandbox Reserved 466: Difference between revisions

The tetanus toxin is composed of 468 amino acid residues. The secondary structures present are alpha helices, 3^10 helices, and beta sheets. Twenty-seven percent of the secondary structures are <scene name='Sandbox_Reserved_466/Alpha_and_3-10_helices/1'>alpha helices and 3^10 helices</scene>, which includes a total of 13 helices (127 residues). The <scene name='Sandbox_Reserved_466/Beta_sheets/1'>beta sheets</scene> make up 17% of the secondary structures in this neurotoxin. This includes 25 strands consists 81 residues [PDB]. The <scene name='Sandbox_Reserved_466/Hydrophobic_residues/1'>hydrophobic residues</scene> exist throughout the protein and on the exterior surface to interact with the lipid molecules of the vesicles.

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].