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 (resides 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. For more details see [[Clostridium Botulinum Neurotoxin Type B]].
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'''Botulinum neurotoxin''' (CBN) is produced by the bacterium ''Clostridium botulinum''. CBP contains a light (residues 1-440) and a heavy (resides 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. The bacteria produces 8 neurotoxins which differ in their antigens.<br />
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*'''Botulinum neurotoxin type A''' is the potent disease agent in botulism.<br />
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*'''Botulinum neurotoxin type B''' is used for treatment of severe spasms in the neck muscles [[Clostridium Botulinum Neurotoxin Type B]]. <br />
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*'''Botulinum neurotoxin type C''' induces apoptotic cell death in cerebellar neurons acting in birds, mammals and fish.<br />
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*'''Botulinum neurotoxin type D''' inhibits the release of TNF from monocytes.<br />
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*'''Botulinum neurotoxin type E, F and G''' act on human proteins of the neuroexocytosis apparatus.<br />
== Disease ==
== Disease ==
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== Structural highlights ==
== Structural highlights ==
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CBP HC contains two modules: the N-terminal translocation domain and the C-terminal receptor-binding domain (residues 876-1296).
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CBP contains a light or catalytic domain (residues 1-440) and a heavy (resides 441-1296) chains (LC and HC). CBP HC contains two modules: the N-terminal translocation domain (residues 441-875) and the C-terminal receptor-binding domain (residues 876-1296).
</StructureSection>
</StructureSection>
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*'''Type A '''
*'''Type A '''
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**[[3bta]], [[4ej5]] – CbCBN + Zn – ''Clostridium botulinum'' <br />
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**[[3bta]] – CbCBN + Zn – ''Clostridium botulinum'' <br />
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**[[3v0c]], [[4el4]], [[4elc]] - CbCBN (mutant) + Zn<br />
+
**[[3v0c]] - CbCBN (mutant) + Zn<br />
**[[2nyy]], [[2nz9]] - CbCBN + antibody + Zn<br />
**[[2nyy]], [[2nz9]] - CbCBN + antibody + Zn<br />
**[[3v0a]], [[3v0b]] - CbCBN (mutant) + antibody + Type A progenitor toxin + Zn<br />
**[[3v0a]], [[3v0b]] - CbCBN (mutant) + antibody + Type A progenitor toxin + Zn<br />
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*Type A Light Chain
*Type A Light Chain
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**[[2g7k]], [[2g7p]], [[2g7q]], [[2imc]], [[3bwi]], [[3bok]], [[3qix]], [[2ise]], [[2isg]], [[2ish]] - CbCBN LC + Zn<br />
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**[[2g7k]], [[2g7p]], [[2g7q]], [[2imc]], [[3bwi]], [[3bok]], [[3qix]], [[2ise]], [[2isg]], [[2ish]], [[4ej5]] - CbCBN LC + Zn<br />
**[[3bok]] - CbCBN LC <br />
**[[3bok]] - CbCBN LC <br />
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**[[1e1h]], [[1xtf]], [[4kuf]] - CbCBN LC (mutant) + Zn<br />
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**[[1e1h]], [[1xtf]], [[4kuf]], [[4el4]], [[4elc]] - CbCBN LC (mutant) + Zn<br />
**[[3dse]] – CbCBN LC (mutant) + Zn + Ni<br />
**[[3dse]] – CbCBN LC (mutant) + Zn + Ni<br />
**[[1xtg]] - CbCBN LC (mutant) + synaptosomal-associated protein 25 + Zn<br />
**[[1xtg]] - CbCBN LC (mutant) + synaptosomal-associated protein 25 + Zn<br />
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**[[4jra]] – CbCBN + synaptic vesicle glycoprotein 2C<br />
**[[4jra]] – CbCBN + synaptic vesicle glycoprotein 2C<br />
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*Type A Light+Heavy Chains
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*Type A Light+Heavy Chain translocation domain
**[[2w2d]] - CbCBN LC+HC + Zn<br />
**[[2w2d]] - CbCBN LC+HC + Zn<br />
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*'''Type B'''
*'''Type B'''
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**[[1s0b]], [[1s0c]], [[1s0d]], [[1s0e]], [[1s0f]], [[1s0g]], [[1epw]], [[1f82]] – CbCBN + Zn<br />
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**[[1s0b]], [[1s0c]], [[1s0d]], [[1s0e]], [[1s0f]], [[1s0g]], [[1epw]] – CbCBN + Zn<br />
**[[2np0]] – CbCBN + synaptotagmin-2 + Zn<br />
**[[2np0]] – CbCBN + synaptotagmin-2 + Zn<br />
**[[1g9a]], [[1g9b]], [[1g9c]], [[1g9d]] – CbCBN + inhibitor + Zn<br />
**[[1g9a]], [[1g9b]], [[1g9c]], [[1g9d]] – CbCBN + inhibitor + Zn<br />
**[[1i1e]] – CbCBN + doxorubicin + Zn<br />
**[[1i1e]] – CbCBN + doxorubicin + Zn<br />
**[[1f31]] – CbPBN + trisaccharide + Zn<br />
**[[1f31]] – CbPBN + trisaccharide + Zn<br />
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**[[1z0h]] – CbCBN C terminal<br />
 
*Type B Light Chain
*Type B Light Chain
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**[[2etf]], [[3zuq]] - CbCBN LC + Zn<br />
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**[[2etf]], [[1f82]] - CbCBN LC + Zn<br />
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*Type B Light+Heavy Chains
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*Type B Light+Heavy Chain translocation domain
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**[[2xhl]] - CbCBN LC+HC + Zn<br />
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**[[2xhl]], [[3zuq]] - CbCBN LC+HC + Zn<br />
*Type B receptor-binding domain
*Type B receptor-binding domain
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**[[2nm1]], [[4kbb]] - CbCBN + synaptotagmin-2<br />
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**[[2nm1]], [[4kbb]] - CbCBN + synaptotagmin-2 peptide<br />
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**[[1z0h]] – CbCBN <br />
*Type C Light Chain
*Type C Light Chain
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*Type E
*Type E
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**[[1t3a]], [[3ffz]] CbCBN + Zn<br />
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**[[3ffz]] – CbCBN + Zn<br />
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*Type E Light Chain
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**[[1t3a]] - CbCBN LC + Zn<br />
**[[1t3c]], [[1zkw]], [[1zkx]], [[1zl5]], [[1zl6]], [[1zn3]] – CbCBN (mutant) + Zn<br />
**[[1t3c]], [[1zkw]], [[1zkx]], [[1zl5]], [[1zl6]], [[1zn3]] – CbCBN (mutant) + Zn<br />

Revision as of 10:22, 12 November 2015

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

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3D structures of botulinum neurotoxin

Updated on 12-November-2015


References

Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky

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