Article Review: Botulinum Toxin; Structure and Mechanism of Action

Authors

DOI:

https://doi.org/10.55544/sjmars.3.6.5

Keywords:

Botulinum toxin, Neurotoxin, Gram positive, exotoxins, BOTOX

Abstract

The anaerobic, Gram-positive bacteria Clostridium botulinum produces a neurotoxin known as botulinum toxin (BoNTs). In this review, the botulinum toxin's chemical makeup, mode of action, and various uses—particularly medical ones—are discussed. The induction of flaccid paralysis by botulinum neurotoxins (BoNT) requires internalization of neural cells, translocation of the catalytic domain into the cytosol, and cleavage of one of the three soluble N-ethylmaleimide sensitive factor attachment protein receptors (SNARE). By blocking nerve signals from reaching muscles, botulinum toxin temporarily weakens muscles. An acute paralytic illness known as botulism can result from accidentally consuming high amounts of botulinum toxin, such as from inadequately canned foods. Botulinum toxins are now used to treat a wide range of medical problems, including strabismus, focal dystonias, hemifacial spasm, other spastic movement disorders, migraines, hypersalivation, and hyperhidrosis, as well as numerous chronic ailments that only partially respond to medical treatment. The FDA authorized the use of Botox® (Botulinum toxin-A) in 2002 for the temporary reduction of glabellar forehead frown lines for cosmetic purposes.

References

[1] Münchau A, Bhatia KP. Uses of botulinum toxin injection in medicine today. BMJ 2000;320:161-5.

[2] Scott AB. Botulinum toxin injection of eye muscles to correct strabismus. Trans Trans Am Ophthalmol Soc 1981;79:734-70.

[3] Ellenhorn MJ, Barceloux DG, editors. Medical Toxicology. Diagnosis and Treatment of Human Poisoning. New York: Elsevier; 1988. p. 1185 7.

[4] Oguma K, Fujinaga Y & Inoue K (1995) Structure and function of Clostridium botulinum toxins. Microbiol Immunol 39, 161–168.

[5] Karalewitz AP, Kroken AR, Fu Z, Baldwin MR, Kim JJ & Barbieri JT (2010) Identification of a unique ganglioside binding loop within botulinum neurotoxins C and D-SA. Biochemistry 49, 8117–8126

[6] Centers for Disease Control and Prevention. 1998. Botulism in the United States (1899–1996). Handbook for epidemiologists, clinicians, and laboratory workers. U.S. Department of Health and Human Services, Atlanta, Ga.

[7] Critchley E, Hayes PJ, Isaacs PE. Outbreak of botulism in the North West of England and Wales. Lancet 1989; 2: 849–853.

[8] Schiavo G, Rossetto O, Tonello F, Montecucco C (1995) Intracellular targets and metalloprotease activity of tetanus and botulism neurotoxins. Curr Top Microbiol Immunol, 195: 257-274.

[9] Halpern JL, Neale EA (1995) Neurospecific binding, internalization, and retrograde axonal transport. Curr Top Microbiol Immunol, 195: 221-241.

[10] Lacy DB, Tepp W, Cohen AC, DasGupta BR & Stevens RC (1998) Crystal structure of botulinum neurotoxin type A and implications for toxicity. Nat Struct Biol 5, 898–902.

[11] Swaminathan S & Eswaramoorthy S (2000) Structural analysis of the catalytic and binding sites of Clostridium botulinum neurotoxin B. Nat Struct Biol 7, 693–699.

[12] Lacy DB & Stevens RC (1999) Sequence homology and structural analysis of clostridial neurotoxins. J Mol Biol 291, 1091–1104.

[13] Umland TC, Wingert LM, Swaminathan S, Furey WF, Schmidt JJ & Sax M (1997) Structure of the receptor binding fragment Hc of tetanus neurotoxin. Nat Struct Biol 4, 788–792.

[14] Murzin AG, Lesk AM & Chothia C (1992) betaTrefoil fold. Patterns of structure and sequence in the Kunitz inhibitors interleukins-1beta and 1alpha and fibroblast growth factors. J Mol Biol 223, 531–543

[15] Muraro L, Tosatto S, Motterlini L, Rossetto O & Montecucco C (2009) The N-terminal half of the receptor domain of botulinum neurotoxin A binds to microdomains of the plasma membrane. Biochem Biophys Res Commun 380, 76–80.

[16] Eswaramoorthy S, Kumaran D, Keller J & SwaminathanS (2004) Role of metals in the biological activity of Clostridium botulinum neurotoxins. Biochemistry 43, 2209–2216

[17] Matthews BW (1988) Structural basis of the action of thermolysin and related zinc peptides. Acc Chem Res 21, 333–340.

[18] Agarwal R, Eswaramoorthy S, Kumaran D, Binz T & Swaminathan S (2004) Structural analysis of botulinum neurotoxin type E catalytic domain and its mutant Glu212 fi Gln reveals the pivotal role of the Glu212 carboxylate in the catalytic pathway. Biochemistry 43, 6637–6644.

[19] Breidenbach MA & Brunger AT (2005) 2.3 A˚ crystal structure of tetanus neurotoxin light chain. Biochemistry 44, 7450–7457.

[20] Vallee BL & Auld DS (1990) Zinc coordination, function, and structure of zinc enzymes and other proteins. Biochemistry 29, 5647–5659.

[21] Fu F, Lomneth RB, Cai S & Singh BR (1998) Role of zinc in the structure and toxic activity of botulinum neurotoxin. Biochemistry 37, 5267–5278.

[22] Simpson LL, Maksymowych AB & Hao S (2001) The role of zinc binding in the biological activity of botulinum toxin. J Biol Chem 276, 27034–27041

[23] Halpern JL, Neale EA (1995) Neurospecific binding, internalization, and retrograde axonal transport. Curr Top Microbiol Immunol, 195: 221-241.

[24] Brin MF (1997) Botulinum toxin: chemistry, pharmacology, toxicity and immunology. Muscle Nerve, Suppl 6: S146-S168.

[25] Rizo J, Sudhof TC. Mechanics of membrane fusion. Nat Struct Biol 1998;5:839-842.

[26] Blasi J, Chapman ER, Link E, et al. Botulinum neurotoxin: a selectively cleaves the synaptic protein SNAP-25. Nature 1993;365:160-163.

[27] Paiva A, Meunier FA, Molgo J, Aoki KR, Dolly JO. Functional repair of motor endplates after botulinum neurotoxin type Apoisoning: biphasic switch of synaptic activity between nerve sprouts and their parent terminals. Proc Natl Acad Sci USA 1999;96:3200-3205.

[28] Swaminathan,S.. (2011). Molecular structures and functional relationships in clostridial neurotoxins. FEBS Journal 278 (2011) 4467–4485

[29] Foster KA (2009) Engineered toxins: new therapeutics. Toxicon 54, 587–592.

[30] Chen S & Barbieri JT (2009) Engineering botulinum neurotoxin to extend therapeutic intervention. Proc Natl Acad Sci 106, 9180–9184

[31] Dolly JO. Therapeutic and research exploitation of botulinum neurotoxins. Eur J Neurol 1997;4: S5- 10

[32] Cuillière C, Ducrotté P, Zerbib F, Metman EH, de Looze D, Guillemot F, et al. Achalasia: Outcome of patients treated with intrasphincteric injection of botulinum toxin. Gut 1997;41:87-92.

[33] Naumann M, Zellner M, Toyka KV, Reiners K. Treatment of gustatory sweating with botulinum toxin. Ann Neurol 1997;42:973-5.

[34] P. Nigam, A. Nigam,2010. Botulinum toxin. Indian Journal of Dermatology. Volume : 55 | Issue : 1 | Page : 8--14

[35] Mazzuco R, Hexsel D. Gummy smile and botulinum toxin: a new approach based on the gingival exposure area. J Am Acad Dermatol. 2010 Dec;63(6):1042-51.

[36] Pontes HA, Pontes FS, Oliveira GF, Almeida HA, Guimarães DM, Cavallero FC. Uncommon foreign body reaction caused by botulinum toxin. J Craniofac Surg. 2012 Jul;23(4):

[37] Bakheit AM, Severa S, Cosgrove A, et al. Safety profile and the efficacy of botulinum toxin a (Dysport) in children with muscle spasticity. Dev Med Child Neurol 2001; 43: 234–238.

Downloads

Published

2024-12-31

How to Cite

Khalaf, Z. Z. (2024). Article Review: Botulinum Toxin; Structure and Mechanism of Action. Stallion Journal for Multidisciplinary Associated Research Studies, 3(6), 92–99. https://doi.org/10.55544/sjmars.3.6.5

Similar Articles

You may also start an advanced similarity search for this article.