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== Structure ==
== Structure ==
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BTX is produced as a single chain protein in the bacterium, but becomes active when a protease cuts the protein into a heavy and light chain connected by a single disulfide bong. The heavy chain is approximately 100 kDa and the light chain is 50 kDa.
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BTX is produced as a single chain protein in the bacterium, but becomes active when a protease cuts the protein into a heavy and light chain connected by a single disulfide bong. The heavy chain is approximately 100 kDa and the light chain is 50 kDa (for reviews about structure see references <ref>Sakaguchi G. 1983. Clostridium botulinum toxins. Pharmacol. Ther. 19:165–
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94. </ref> <ref> Minton NP. 1995. Molecular genetics of
 +
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–
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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.
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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BTX also has two associated auxiliary proteins: hemagglutinins (HA) and nonhemagglutinin (NTNH). HA and NTNH do not directly play a role in the toxic effect of BTX, but have an indirect role during ingestion of the protein by making the BTX more resistant to low pH environments and proteolytic enzymes found in the gut.
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BTX also has two auxiliary proteins that compromise a multimeric complex: hemagglutinins (HA) and nonhemagglutinin (NTNH). HA and NTNH do not directly play a role in the toxic effect of BTX, but have an indirect role during ingestion of the protein by making the BTX more resistant to low pH environments and proteolytic enzymes found in the gut.
== Function ==
== Function ==

Revision as of 18:47, 24 April 2016

Contents

Background

Botulinum Toxin (BTX) is produced by three species of obligate anaerobe bacterium, primarily Clostridium botulism, but Clostridium baratii and Clostridium butyricum also produce the protein [1] [2] [3]. Clostridium botulism is commonly found in soil, marine sediments, and the gut of grazing animals [4] [5] [6] [7] [8] . BTX is the protein responsible for causing botulism, a potentially fatal illness. Humans can be exposed to the neurotoxin through inhalation, ingestion, or surface wounds. There are seven forms of the protein, named A through G, that are structurally similar but create different immune responses [9]. The forms of BTX that most often cause botulism in humans are A, B, and E [10].

Botulinum Toxin Neurotoxin Serotype A

Drag the structure with the mouse to rotate

Structure

BTX is produced as a single chain protein in the bacterium, but becomes active when a protease cuts the protein into a heavy and light chain connected by a single disulfide bong. The heavy chain is approximately 100 kDa and the light chain is 50 kDa (for reviews about structure see references [11] [12] [13] [14] [15].

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.

BTX also has two auxiliary proteins that compromise a multimeric complex: hemagglutinins (HA) and nonhemagglutinin (NTNH). HA and NTNH do not directly play a role in the toxic effect of BTX, but have an indirect role during ingestion of the protein by making the BTX more resistant to low pH environments and proteolytic enzymes found in the gut.

Function

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 [16] [17]. 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 [18].


Relevance

Structural Highlights

References

  1. ↑ Hall JD, McCroskey LM, Pincomb BJ, Hatheway CL. Isolation of an organism resembling Clostridium baratii which produces type F botulinal toxin from an infant with botulism. J Clin Microbiol. 1985;21:654-655. 36.
  2. ↑ Aureli P, Fenicia L, Pasolini B, Gianfranceschi M, McCroskey LM, Hatheway CL. Two cases of type E infant botulism caused by neurotoxigenic Clostridium butyricum in Italy. J Infect Dis. 1986;154: 207-211. 37.
  3. ↑ Arnon SS. Botulism as an intestinal toxemia. In: Blaser MJ, Smith PD, Ravdin JI, Greenberg HB, Guerrant RL, eds. Infections of the Gastrointestinal Tract. New York, NY: Raven Press; 1995:257-271.
  4. ↑ Ward BQ, Carroll BJ, Garrett ES, GB Reese. Survey of the U.S. Gulf Coast for the presence of Clostridium botulinum. Appl Microbiol. 1967;15:629–636. 26.
  5. ↑ Smith LDS. The occurrence of Clostridium botulinum and Clostridium tetani in the soil of the United States. Health Lab Sci. 1978;15:74–80. 27.
  6. ↑ Sugiyama H. Clostridium botulinum neurotoxin. Microbiol Rev. 1980;44:419–448. 28. Dodds KL. Clostridium botulinum in the environment. In: Hauschild AHW
  7. ↑ Dodds KL, eds. Clostridium botulinum—Ecology and Control in Foods. New York, NY: Marcel Dekker, Inc; 1992: 21–51. 29.
  8. ↑ Popoff MR. Ecology of neurotoxigenic strains of clostridia. In: Montecucco C, ed. Current Topics in Microbiology: Clostridial Neurotoxins. The Molecular Pathogenesis of Tetanus and Botulism. Vol 195. Berlin, Germany: Springer-Verlag; 1995: 1–29.
  9. ↑ Hatheway cL. Clostridium botulinum and other clostridia that produce botulinum neurotoxins. in: Hauschild aHW, Dodds kL, eds. Clostridium botulinum—Ecology and Control in Foods. new york, ny: marcel Dekker, inc; 1992: 3–10
  10. ↑ arnon SS, Schechter r, inglesby tV, et al. botulinum toxin as a biological weapon: medical and public health management. JAMA. 2001;285:1059–1070.
  11. ↑ Sakaguchi G. 1983. Clostridium botulinum toxins. Pharmacol. Ther. 19:165– 94.
  12. ↑ Minton NP. 1995. Molecular genetics of clostridial neurotoxins. Curr. Top. Microbiol. Immunol. 195:161–94
  13. ↑ Oguma K, Fujinaga Y, Inoue K. 1995.Structure and function of Clostridium botulinum toxins. Microbiol. Immunol. 39:161–68
  14. ↑ Lacy BD, Stevens RC. 1999. Sequence homology and structural analysis of the clostridial neurotoxins. J. Mol. Biol. 291: 1091–104
  15. ↑ Popoff MR, Marvaud J-C. 1999. Structural and genomic features of clostridial neurotoxins. See Ref. 132, pp. 174– 201
  16. ↑  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.
  17. ↑  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.
  18. ↑ Dembek, Z. F.; Smith, L. A.; Rusnak, J. Botulinum Toxin. In Medical Aspects of Biological Warfare; 2007.
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