Botulinum neurotoxin

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== Function ==
== Function ==
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'''Botulinum neurotoxin''' (CBN) is produced by the bacterium ''Clostridium botulinum''. CBP contains a light (residues 1-440) and a heavy (residues 441-875) chains (LC and HC). CBP LC proteolyzes SNARE substrates which are essential for synaptic vescicle fusion and neurotransmitter release thus causing paralysis. CBP HC acts as a channel and as transmembrane chaperone enabling the passage of the LC into the cytosol. <ref>PMID:15907915</ref> The bacteria produces 8 neurotoxins which differ in their antigens.<br />
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'''Botulinum neurotoxin''' (CBN) is produced by the bacterium ''Clostridium botulinum''. CBP contains a light (residues 1-440) and a heavy (residues 441-875) chains (LC and HC). CBP LC proteolyzes SNARE substrates ([[Synaptosomal-associated protein]]-25 or SNAP-25) which are essential for synaptic vesicle fusion and neurotransmitter release thus causing paralysis. CBP HC acts as a channel and as transmembrane chaperone enabling the passage of the LC into the cytosol. <ref>PMID:15907915</ref> The bacteria produces 8 neurotoxins which differ in their antigens.<br /> See also [[Llama Antibody Inhibits Botulinum Neruotoxin|Llama Antibody Inhibits Botulinum Neurotoxin]].
*'''Botulinum neurotoxin type A''' is the potent disease agent in botulism. See [[Clostridium botulinum neurotoxin serotype A light chain]] and [[Botulinum neurotoxin type A (Hebrew)]].<br />
*'''Botulinum neurotoxin type A''' is the potent disease agent in botulism. See [[Clostridium botulinum neurotoxin serotype A light chain]] and [[Botulinum neurotoxin type A (Hebrew)]].<br />
*'''Botulinum neurotoxin type B''' is used for treatment of severe spasms in the neck muscles. See [[Clostridium Botulinum Neurotoxin Type B]]. <br />
*'''Botulinum neurotoxin type B''' is used for treatment of severe spasms in the neck muscles. See [[Clostridium Botulinum Neurotoxin Type B]]. <br />
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== Relevance ==
== Relevance ==
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'''CBP type A''' is used by the cosmetics industry for smoothing wrinkles and is known commercially as Botox. It is used in the treatment of photophobia and Dry Eye<ref>PMID:29110944</ref> and in treatment of individulas with certain pain conditions including migraine<ref>PMID:26879873</ref>. In small quantities CBN can be used as muscle relaxant in cases of spasm and dystonia. '''CBP type E''' delivery to the hippocampus ia antiepileptogenic in models of epilepsy<ref>PMID:15728834</ref>.
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'''CBP type A''' is used by the cosmetics industry for smoothing wrinkles and is known commercially as Botox. It is used in the treatment of photophobia and Dry Eye<ref>PMID:29110944</ref> and in treatment of individuals with certain pain conditions including migraine<ref>PMID:26879873</ref>. In small quantities CBN can be used as muscle relaxant in cases of spasm and dystonia. '''CBP type E''' delivery to the hippocampus ia antiepileptogenic in models of epilepsy<ref>PMID:15728834</ref>.
== Structural highlights ==
== Structural highlights ==
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CBP contains a <scene name='67/671726/Cv/9'>light or catalytic domain</scene> (LC, residues 1-440, in magenta) and a <scene name='67/671726/Cv/10'>heavy</scene> (HC, residues 441-1296, in cyan) chain. CBP HC contains two modules:
CBP contains a <scene name='67/671726/Cv/9'>light or catalytic domain</scene> (LC, residues 1-440, in magenta) and a <scene name='67/671726/Cv/10'>heavy</scene> (HC, residues 441-1296, in cyan) chain. CBP HC contains two modules:
the N-terminal <scene name='67/671726/Cv/11'>translocation domain</scene> (residues 441-875, in salmon) and the C-terminal <scene name='67/671726/Cv/12'>receptor-binding domain</scene> (residues 876-1296, in yellow). <scene name='67/671726/Cv/13'>Cofactor Zn+2 coordination site</scene>. <ref>PMID:9783750</ref>
the N-terminal <scene name='67/671726/Cv/11'>translocation domain</scene> (residues 441-875, in salmon) and the C-terminal <scene name='67/671726/Cv/12'>receptor-binding domain</scene> (residues 876-1296, in yellow). <scene name='67/671726/Cv/13'>Cofactor Zn+2 coordination site</scene>. <ref>PMID:9783750</ref>
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</StructureSection>
 
==3D structures of botulinum neurotoxin==
==3D structures of botulinum neurotoxin==
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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[[Botulinum neurotoxin 3D structures]]
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{{#tree:id=OrganizedByTopic|openlevels=0|
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*'''Type A '''
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</StructureSection>
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**[[3bta]] – CbCBN + Zn – ''Clostridium botulinum'' <br />
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**[[3v0c]] - CbCBN (mutant) + Zn<br />
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**[[2nyy]], [[2nz9]] - CbCBN + antibody + Zn<br />
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**[[3v0a]], [[3v0b]] - CbCBN (mutant) + antibody + Type A progenitor toxin + Zn<br />
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*Type A Light Chain
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**[[2g7k]], [[2g7p]], [[2g7q]], [[2imc]], [[3bwi]], [[3bon]], [[3qix]], [[2ise]], [[2isg]], [[2ish]], [[4ej5]] - CbCBN LC + Zn<br />
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**[[5vgv]] - CbCBN LC + Cu<br />
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**[[5vgx]] - CbCBN LC + Hg<br />
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**[[3bok]] - CbCBN LC <br />
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**[[1e1h]], [[1xtf]], [[4kuf]], [[4el4]], [[4elc]] - CbCBN LC (mutant) + Zn<br />
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**[[3dse]] – CbCBN LC (mutant) + Zn + Ni<br />
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**[[1xtg]] - CbCBN LC (mutant) + synaptosomal-associated protein 25 + Zn<br />
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**[[3dda]], [[3ddb]] - CbCBN LC + synaptosomal-associated protein 25 peptide + Zn<br />
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**[[3zur]], [[3zus]] - CbCBN LC/synaptosomal-associated protein 25 translocation domain<br />
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**[[2g7n]], [[2ilp]], [[2imb]], [[3qiy]], [[3qiz]], [[3qj0]], [[4hev]], [[2ima]], [[5v8r]] – CbCBN LC + inhibitor + Zn<br />
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**[[3c88]], [[3c89]], [[3c8a]], [[3c8b]], [[3boo]], [[3qw5]], [[3qw6]], [[3qw7]], [[3qw8]], [[3nf3]] – CbCBN LC + inhibitor peptide + Zn<br />
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**[[4ks6]], [[4ktx]], [[5v8p]], [[5v8u]] - CbCBN LC (mutant) + inhibitor peptide + Zn<br />
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**[[3ds9]] – CbCBN LC (mutant) + inhibitor peptide + Zn + Ni<br />
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**[[3k3q]] - CbCBN LC + antibody + Zn<br />
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*Type A receptor-binding domain
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**[[2vua]], [[3fuo]], [[5tpb]], [[5tpc]], [[5lr0]], [[5mk6]], [[5mk7]] – CbPBN <br />
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**[[4iqp]] – CbPBN (mutant)<br />
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**[[2vu9]] – CbPBN + polysaccharide + Mg<br />
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**[[4jra]], [[5jlv]], [[5moy]] – CbCBN + synaptic vesicle glycoprotein 2C<br />
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**[[5jmc]] – CbCBN (mutant) + synaptic vesicle glycoprotein 2C<br />
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**[[4zjx]] – CbCBN + polypeptide inhibitor<br />
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**[[5l21]] – CbCBN + VHH-C2<br />
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*Type A Light+Heavy Chain translocation domain
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**[[2w2d]], [[3bta]] - CbCBN LC+HC + Zn<br />
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*'''Type B'''
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**[[1s0b]], [[1s0c]], [[1s0d]], [[1s0e]], [[1s0f]], [[1s0g]], [[1epw]] – CbCBN + Zn<br />
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**[[2np0]] – CbCBN + synaptotagmin-2 + Zn<br />
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**[[1g9a]], [[1g9b]], [[1g9c]], [[1g9d]] – CbCBN + inhibitor + Zn<br />
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**[[1i1e]] – CbCBN + doxorubicin + Zn<br />
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**[[1f31]] – CbPBN + trisaccharide + Zn<br />
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*Type B Light Chain
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**[[2etf]], [[1f82]] - CbCBN LC + Zn<br />
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*Type B Light+Heavy Chain translocation domain
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**[[2xhl]], [[3zuq]] - CbCBN LC+HC + Zn<br />
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*Type B receptor-binding domain
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**[[2nm1]], [[4kbb]] - CbCBN + synaptotagmin-2 peptide<br />
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**[[1z0h]] – CbCBN <br />
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**[[5vid]] – CbCBN + mini-protein binder<br />
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*Type C Light Chain
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**[[2qn0]] - CbCBN LC + Zn<br />
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**[[3deb]] - CbCBN LC (mutant)<br />
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*Type C receptor-binding domain
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**[[3n7k]], [[3r4s]], [[3r4u]] - CbCBN <br />
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*Type D Light Chain
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**[[2fpq]] - CbCBN LC + Zn<br />
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*Type D receptor-binding domain
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**[[3n7j]], [[3obr]], [[3ogg]] - CbCBN <br />
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**[[3rmx]], [[3rmy]] – CbCBN (mutant) <br />
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**[[3obt]] - CbCBN + acetylneuraminic acid<br />
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**[[5bqm]] – CbCBN + somatoliberin<br />
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*Type D LHN domain
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**[[5bqn]] - CbCBN <br />
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*Type DC Heavy Chain
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**[[4isq]] - CbCBN HC + synaptotagmin-1 toxin-binding domain<br />
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**[[4isr]] - CbCBN HC + synaptotagmin-2 toxin-binding domain<br />
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*Type E
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**[[3ffz]], [[4zkt]] – CbCBN + Zn<br />
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*Type E Light Chain
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**[[1t3a]] - CbCBN LC + Zn<br />
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**[[1t3c]], [[1zkw]], [[1zkx]], [[1zl5]], [[1zl6]], [[1zn3]] – CbCBN (mutant) + Zn<br />
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*Type F Light Chain
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**[[2a8a]], [[2a97]] - CbCBN LC + Zn<br />
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**[[3fie]], [[3fii]] - CbCBN LC + Zn + synaptobrevin-2<br />
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*Type F receptor-binding domain
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**[[3rsj]] - CbCBN <br />
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*Type G Light Chain
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**[[1zb7]] - CbCBN LC + Zn<br />
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*Type G receptor-binding domain
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**[[2vxr]], [[3mpp]] - CbCBN <br />
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*Type X Light Chain
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**[[6f4e]] - CbCBN LC<br />
 
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**[[6f47]] - CbCBN LC + Zn<br />
 
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}}
 
[[Category: Topic Page]]
[[Category: Topic Page]]

Current revision

Clostridium botulinum neurotoxin type A with cofactor Zn+2 (grey) (PDB code 3bta).

Drag the structure with the mouse to rotate


References

  1. ↑ Montecucco C, Molgo J. Botulinal neurotoxins: revival of an old killer. Curr Opin Pharmacol. 2005 Jun;5(3):274-9. PMID:15907915 doi:http://dx.doi.org/10.1016/j.coph.2004.12.006
  2. ↑ Karalewitz AP, Fu Z, Baldwin MR, Kim JJ, Barbieri JT. Botulinum neurotoxin serotype C associates with dual ganglioside receptors to facilitate cell entry. J Biol Chem. 2012 Nov 23;287(48):40806-16. doi: 10.1074/jbc.M112.404244. Epub, 2012 Oct 1. PMID:23027864 doi:http://dx.doi.org/10.1074/jbc.M112.404244
  3. ↑ Zhang S, Berntsson RP, Tepp WH, Tao L, Johnson EA, Stenmark P, Dong M. Structural basis for the unique ganglioside and cell membrane recognition mechanism of botulinum neurotoxin DC. Nat Commun. 2017 Nov 21;8(1):1637. doi: 10.1038/s41467-017-01534-z. PMID:29158482 doi:http://dx.doi.org/10.1038/s41467-017-01534-z
  4. ↑ Zhang S, Masuyer G, Zhang J, Shen Y, Lundin D, Henriksson L, Miyashita SI, Martinez-Carranza M, Dong M, Stenmark P. Identification and characterization of a novel botulinum neurotoxin. Nat Commun. 2017 Aug 3;8:14130. doi: 10.1038/ncomms14130. PMID:28770820 doi:http://dx.doi.org/10.1038/ncomms14130
  5. ↑ Diel RJ, Kroeger ZA, Levitt RC, Sarantopoulos C, Sered H, Martinez-Barrizonte J, Galor A. Botulinum Toxin A for the Treatment of Photophobia and Dry Eye. Ophthalmology. 2018 Jan;125(1):139-140. doi: 10.1016/j.ophtha.2017.09.031. Epub, 2017 Oct 27. PMID:29110944 doi:http://dx.doi.org/10.1016/j.ophtha.2017.09.031
  6. ↑ Patil S, Willett O, Thompkins T, Hermann R, Ramanathan S, Cornett EM, Fox CJ, Kaye AD. Botulinum Toxin: Pharmacology and Therapeutic Roles in Pain States. Curr Pain Headache Rep. 2016 Mar;20(3):15. doi: 10.1007/s11916-016-0545-0. PMID:26879873 doi:http://dx.doi.org/10.1007/s11916-016-0545-0
  7. ↑ Costantin L, Bozzi Y, Richichi C, Viegi A, Antonucci F, Funicello M, Gobbi M, Mennini T, Rossetto O, Montecucco C, Maffei L, Vezzani A, Caleo M. Antiepileptic effects of botulinum neurotoxin E. J Neurosci. 2005 Feb 23;25(8):1943-51. doi: 10.1523/JNEUROSCI.4402-04.2005. PMID:15728834 doi:http://dx.doi.org/10.1523/JNEUROSCI.4402-04.2005
  8. ↑ Lacy DB, Tepp W, Cohen AC, DasGupta BR, Stevens RC. Crystal structure of botulinum neurotoxin type A and implications for toxicity. Nat Struct Biol. 1998 Oct;5(10):898-902. PMID:9783750 doi:10.1038/2338

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