• The toxin produced from Clostridium tetani, which causes tetanus, is a protease that cleaves and destroys SNAREs. Explain why this activity would lead to paralysis.

 

• Many ABC transporters are inhibited by vanadate, a phosphate analog. Why is vanadate an effective inhibitor of these transporters?

 

Clostridium tetani is bacteria causing tetanus. The bacteria releases clostridial neurotoxins responsible for botulism and tetanus comprising of three domains with different functions: proteolysis, neurospecific binding and membrane translocation of the neuroexocytosis. The neurotoxin binds to the neuromuscular junction's presynaptic membrane and transported to the spinal cord retroaxonally by motor neurons. The neurotoxins block the release of neurotransmitter from the spinal inhibitory interneurons. This usually suppresses muscular activities and motor neuron resulting in the enhanced excitability and activation of the motor neurons, which are affected. The botulin neurotoxins induce a flaccid paralysis by inhibiting the release of acetylcholine from the muscular junction. Widespread intoxication causes continuous involuntary muscle contractions. The local internalization can result in muscle hypersensitivity.

The ABC transporters are one of the largest active transport systems of the cell. Vanadate is a phosphate analog that inhibits the transport of maltose by trapping ADP is one of the nucleotide-binding sites of the membrane transporter after ATP hydrolysis. Vanadate can mimic the transition state of the y-phosphate of ATP during hydrolysis.