Sandbox Reserved 403: Difference between revisions

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<Structure load='1fv2' size='500' frame='true' align='right' caption='THE HC FRAGMENT OF TETANUS TOXIN COMPLEXED WITH AN ANALOGUE OF ITS GANGLIOSIDE RECEPTOR GT1B' scene='Insert optional scene name here' />
<Structure load='1fv2' size='500' frame='true' align='right' caption='THE HC FRAGMENT OF TETANUS TOXIN COMPLEXED WITH AN ANALOGUE OF ITS GANGLIOSIDE RECEPTOR GT1B' scene='Insert optional scene name here' />


== Clostidiuam tetani ==


The gram positive bacilli Clostridium tetani is the bacteria responsible for the disease state of tetanus.  The presence of the bacteria does not cause the disease but instead the toxins it produces cause the disease state.  C. tetani produces two toxins; tetanospasmin and tetanolysin. The role or function of tetanolysin is unknown but it is believed to assist tetanospasmin.  Tetanospasmin is the cause of tetanus and is sometimes referred to as tetanus neurotoxin (TeNT), as it acts on the central nervous system.  Tetanospasmin makes its way to the central nervous system via retrograde axonal flow beginning with α- motor neurons found in muscle and ending by binding to gangliosides found in the central nervous system.
The gram positive bacilli Clostridium tetani is the bacteria responsible for the disease state of tetanus.  The presence of the bacteria does not cause the disease but instead the toxins it produces cause the disease state.  C. tetani produces two toxins; tetanospasmin and tetanolysin. Tetanolysin is a cytolysin that increases the permeability of cellular membranes.  Tetanospasmin is the cause of tetanus and is sometimes referred to as tetanus neurotoxin (TeNT), as it acts on the central nervous system.  Tetanospasmin makes its way to the central nervous system via retrograde axonal flow beginning with α- motor neurons found in muscle and ending by binding to gangliosides found in the central nervous system.
 
 
== Gangliosides ==


Gangliosides are in the category of glycosphingolipids and are found predominately in neuronal tissues.  Gangliosides consist of sialic acid linked to a sugar (glucose, galactose, GalNAc, GlcNAc and/or fructose) backbone attached to a ceramide base. These gangliosides make up approximately 10% of a neuron’s
Gangliosides are in the category of glycosphingolipids and are found predominately in neuronal tissues.  Gangliosides consist of sialic acid linked to a sugar (glucose, galactose, GalNAc, GlcNAc and/or fructose) backbone attached to a ceramide base. These gangliosides make up approximately 10% of a neuron’s
total lipid content and like other lipids functions in cell signal transduction.
total lipid content and like other lipids functions in cell signal transduction.
== Tetanospasmin (TeNT) ==


Tetanospasmin is a 150-kDa toxin that is composed of one light chain (50-kDa) and one heavy chain (100-kDa).  The light chain is responsible for the toxicity of the molecule, whereas the heavy chain is responsible for binding the toxin to the axonal membranes.  The heavy chain can also be cleaved into 2 fragments HN and HC.  The HN fragment is responsible for the translocation of the light chain across the axonal membrane, whereas the HC fragment binds to the axonal membrane.
Tetanospasmin is a 150-kDa toxin that is composed of one light chain (50-kDa) and one heavy chain (100-kDa).  The light chain is responsible for the toxicity of the molecule, whereas the heavy chain is responsible for binding the toxin to the axonal membranes.  The heavy chain can also be cleaved into 2 fragments HN and HC.  The HN fragment is responsible for the translocation of the light chain across the axonal membrane, whereas the HC fragment binds to the axonal membrane.
   
   
== Hc and Ganglioside Interaction ==
Hc has two distinct domains:   
Hc has two distinct domains:   
1. Jelly-roll (amino end)
1. Jelly-roll (amino end)
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The Hc fragment has two binding sites in the β-trefoil domain:
The Hc fragment has two binding sites in the β-trefoil domain:
1. Gal-4-GalNAc3-forming a narrow groove where a number of hydrogen bonds can form.  
 
Common hydrogen bonds are formed between the side
1.Gal-4-GalNAc3-forming a narrow groove where a number of hydrogen bonds can form. Common hydrogen bonds are formed between the side chain of His1271 and OH-6, OH-4 and O-5 of Gal4 and between
chain of His1271 and OH-6, OH-4 and O-5 of Gal4 and between
the main chain carbonyl oxygen of Thr1270 and OH-4 of Gal4.
the main chain carbonyl oxygen of Thr1270 and OH-4 of Gal4.
GalNAc3 interacts via a hydrogen bond between OH-4 andAsp1222 OD and between OH-4 and His1271. Ring stacking involving galactose also occurs in this site.  
GalNAc3 interacts via a hydrogen bond between OH-4 andAsp1222 OD and between OH-4 and His1271. Ring stacking involving galactose also occurs in this site.  
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