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Neurotoxin. Mamba snake. Why Fasciculin ?. Mambas have only Fasciculin Fasciculins : a family of closely related peptides isolated from Mamba venom toxins (FAS-I, FAS-II, and FAS-III)

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neurotoxin

Neurotoxin

Mamba snake

why fasciculin
Why Fasciculin?
  • Mambas have only Fasciculin
  • Fasciculins : a family of closely related peptides isolated from Mamba venom toxins (FAS-I, FAS-II, and FAS-III)
  • Function : Inhibits ACETYLCHOLINESTERASE (AChE), which is an enzyme to degrade neurotransmitter ACh. In skeletal muscle, fasciculations are observed initially, followed by flaccid paralysis.
about fasciculin
About Fasciculin
  • Small protein (61 amino acids)
  • 3-finger shaped
  • Cross-linked by 4 disulfide bridges

(S atoms are in Cystine amino acid)

mode of action
Mode of Action

The snake neurotoxins act on the neuromuscular junction and block neuromuscular transmission.

  • Fasciculin interferes with this process by binding to Acetylcholinesterase (AChE).
  • Result: “Death by respiratory paralysis”.
receptors as targets
Receptors as Targets
  • Antagonists: prevent receptor activation
  • Agonists: stimulate then inactivate
  • Acetylcholinesterase inhibitors: prevent degradation

Mechanism: By inhibiting acetylcholinesterase and pseudocholinesterase, this neurotoxin allows ACh to build up at its receptors. Thus, they result in enhancement of both muscarinic and nicotinic agonist effect

neuromuscular junction
Neuromuscular Junction

Vesicles containing

Acetylcholine (ACh)

ACh receptors

Acetylcholinesterase

(AChE)

mechanism of enzyme action
Mechanism of Enzyme Action
  • Lock and Key Theory states that “a substrate has a shape fitting that of the enzyme’s active side, as a key fits a lock”. “The lock is the enzyme and the key is the substrate”

(Mechanism of Enzyme Action)

  • Induced-Fit Theory states that “the conformation of an enzyme changes to accommodate an incoming substrate”.
acetylcholinesterase
Acetylcholinesterase
  • Enzyme which breaks downacetylcholine neurotransmitter
    • acetylcholinesterase inhibitors = neurotoxins

neurotoxin in green

active site in red

snake toxin blockingacetylcholinesterase active site

acetylcholinesterase

acetycholinesterase cleans up
Acetycholinesterase Cleans Up
  • AChEhydrolizesACh, so that the process can start again.
irreversible inhibitors
Irreversible Inhibitors
  • Bind to the active site of the enzyme.
  • Exhibit concentration-dependent inhibition: the more inhibitor, the greater the inhibition of the enzyme.
  • Inhibition cannot be reversed by adding more substrate.
  • Usually resemble the substrate in chemical structure somewhat.
structure function of fasciculin
Structure/Function of Fasciculin
  • Acetylcholinesterase with Acetylcholine bound.Red = AChE active siteYellow = ACh molecule