Sandbox WWC1: Difference between revisions

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clostridial neurotoxins. Curr. Top. Microbiol.

Immunol. 195:161–94 </ref> <ref> Oguma K, Fujinaga Y, Inoue K. 1995.Structure and function of Clostridium botulinum toxins. Microbiol. Immunol. 39:161–68 </ref> <ref> Lacy BD, Stevens RC. 1999. Sequence homology and structural analysis of the clostridial neurotoxins. J. Mol. Biol. 291: 1091–104 </ref> <ref> Popoff MR, Marvaud J-C. 1999. Structural and genomic features of clostridial neurotoxins. See Ref. 132, pp. 174–

201 </ref>.

201 </ref>).

The light chain contains the consensus sequence HELIH that codes for the binding of zinc, which subsequently regulates the endopeptidase activity of the light chain.

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== Function ==

The active form of BTX has three functional domains responsible for binding, translocation, and catalysis <ref>Montecucco and Schiavo 1995 C. Montecucco, G. Schiavo Structure and function of tetanus and botulinum neurotoxins Quart. Rev. Biophys., 28 (1995), pp. 423–472. </ref>. The C terminus of the heavy chain is responsible for binding a ganglioside and protein receptors on the nerve terminal while the N terminus half functions by translocating the protein across the membrane by signaling endocytosis <ref>Dolly et al 1984 J.O. Dolly, J. Black, R.S. Williams, J. Melling Acceptors for botulinum neurotoxin reside on motor nerve terminals and mediate its internalization Nature, 307 (1984), pp. 457–460 </ref>. Once in a vesicle in the cytosol of a nerve terminal, the light chain dissociates from the heavy chain and cleaves SNARE proteins involved in synaptic vesicle fusion. The cleavage of these SNARE proteins, VAMP, SNAP-25, and syntax, depends on the serotype of BTX where each serotype cuts at a different place. The cut SNAREs inhibit the binding of vesicles containing acetylcholine which effectively stops the signaling from nerves to muscle cells, resulting in paralysis <ref>Lacy, D. B.; Stevens, R. C. Sequence Homology and Structural Analysis of the Clostridial neurotoxins1. J. Mol. Biol. 1999, 291 (5), 1091–1104.

</ref>.

== Disease ==

Botulism is characterized by paralysis due to the interference of BTX with the release of acetylcholine at nerve synapses. The lethal doses for a human weighing 70 kg is 0.09-0.15 μg when administered intravenously or intramuscularly, 0.70 - 0.90 μg through inhalation, and 70 μg orally <ref>  Franz DR, Pitt LM, Clayton MA, Hanes MA, Rose KJ. Efficacy of prophylactic and therapeutic administration of antitoxin for inhalation botulism. In: DasGupta BR, ed. Botulinum and Tetanus Neurotoxins: Neurotransmission and Biomedical Aspects. New York, NY: Plenum Press; 1993:473-476. </ref> <ref>  Herrero BA, Ecklung AE, Streett CS, Ford DF, King JK. Experimental botulism in monkeys: a clinical pathological study. Exp Mol Pathol. 1967;6:84-95.</ref>. Due to its powerful toxicity, the protein could be used as a biological weapon. The countries that have developed BTX to be used in warfare include Japan, Germany, United States, Russia, and Iraq <ref> Dembek, Z. F.; Smith, L. A.; Rusnak, J. Botulinum Toxin. In Medical Aspects of Biological Warfare; 2007. </ref>.

Sandbox WWC1: Difference between revisions

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@@ Line 10: / Line 10: @@
 clostridial neurotoxins. Curr. Top. Microbiol.
 Immunol. 195:161–94 </ref> <ref> Oguma K, Fujinaga Y, Inoue K. 1995.Structure and function of Clostridium botulinum toxins. Microbiol. Immunol. 39:161–68 </ref> <ref>  Lacy BD, Stevens RC. 1999. Sequence homology and structural analysis of the clostridial neurotoxins. J. Mol. Biol. 291: 1091–104 </ref> <ref>  Popoff MR, Marvaud J-C. 1999. Structural and genomic features of clostridial neurotoxins. See Ref. 132, pp. 174–
-</ref>.
+</ref>).
 The light chain contains the consensus sequence HELIH that codes for the binding of zinc, which subsequently regulates the endopeptidase activity of the light chain.
@@ Line 17: / Line 17: @@
 == Function ==
+The active form of BTX has three functional domains responsible for binding, translocation, and catalysis <ref>Montecucco and Schiavo 1995 C. Montecucco, G. Schiavo Structure and function of tetanus and botulinum neurotoxins Quart. Rev. Biophys., 28 (1995), pp. 423–472. </ref>. The C terminus of the heavy chain is responsible for binding a ganglioside and protein receptors on the nerve terminal while the N terminus half functions by translocating the protein across the membrane by signaling endocytosis <ref>Dolly et al 1984 J.O. Dolly, J. Black, R.S. Williams, J. Melling Acceptors for botulinum neurotoxin reside on motor nerve terminals and mediate its internalization Nature, 307 (1984), pp. 457–460 </ref>. Once in a vesicle in the cytosol of a nerve terminal, the light chain dissociates from the heavy chain and cleaves SNARE proteins involved in synaptic vesicle fusion. The cleavage of these SNARE proteins, VAMP, SNAP-25, and syntax, depends on the serotype of BTX where each serotype cuts at a different place. The cut SNAREs inhibit the binding of vesicles containing acetylcholine which effectively stops the signaling from nerves to muscle cells, resulting in paralysis <ref>Lacy, D. B.; Stevens, R. C. Sequence Homology and Structural Analysis of the Clostridial neurotoxins1. J. Mol. Biol. 1999, 291 (5), 1091–1104.
+</ref>.
 == Disease ==
 Botulism is characterized by paralysis due to the interference of BTX with the release of acetylcholine at nerve synapses. The lethal doses for a human weighing 70 kg is 0.09-0.15 μg when administered intravenously or intramuscularly, 0.70 - 0.90 μg through inhalation, and 70 μg orally <ref> 	Franz DR, Pitt LM, Clayton MA, Hanes MA, Rose KJ. Efficacy of prophylactic and therapeutic administration of antitoxin for inhalation botulism. In: DasGupta BR, ed. Botulinum and Tetanus Neurotoxins: Neurotransmission and Biomedical Aspects. New York, NY: Plenum Press; 1993:473-476. </ref> <ref> 	Herrero BA, Ecklung AE, Streett CS, Ford DF, King JK. Experimental botulism in monkeys: a clinical pathological study. Exp Mol Pathol. 1967;6:84-95.</ref>. Due to its powerful toxicity, the protein could be used as a biological weapon. The countries that have developed BTX to be used in warfare include Japan, Germany, United States, Russia, and Iraq <ref> Dembek, Z. F.; Smith, L. A.; Rusnak, J. Botulinum Toxin. In Medical Aspects of Biological Warfare; 2007. </ref>.