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==Crystal structure of the catalytic domain of Botulinum neurotoxin serotype a with a snap-25 peptide==
==Crystal structure of the catalytic domain of Botulinum neurotoxin serotype a with a snap-25 peptide==
<StructureSection load='3dda' size='340' side='right' caption='[[3dda]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
<StructureSection load='3dda' size='340' side='right'caption='[[3dda]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3dda]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_botulinus"_van_ermengem_1896 "bacillus botulinus" van ermengem 1896]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DDA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3DDA FirstGlance]. <br>
<table><tr><td colspan='2'>[[3dda]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridium_botulinum Clostridium botulinum] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DDA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DDA FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.5&#8491;</td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3bwi|3bwi]], [[3c88|3c88]], [[3c89|3c89]], [[3c8a|3c8a]], [[3c8b|3c8b]], [[3ddb|3ddb]]</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3dda FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dda OCA], [https://pdbe.org/3dda PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3dda RCSB], [https://www.ebi.ac.uk/pdbsum/3dda PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3dda ProSAT]</span></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">botA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1491 "Bacillus botulinus" van Ermengem 1896])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Bontoxilysin Bontoxilysin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.69 3.4.24.69] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3dda FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dda OCA], [http://pdbe.org/3dda PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3dda RCSB], [http://www.ebi.ac.uk/pdbsum/3dda PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3dda ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/BXA1_CLOBH BXA1_CLOBH]] Inhibits acetylcholine release. The botulinum toxin binds with high affinity to peripheral neuronal presynaptic membrane to the secretory vesicle protein SV2. It binds directly to the largest luminal loop of SV2A, SV2B and SV2C. It is then internalized by receptor-mediated endocytosis. The C-terminus of the heavy chain (H) is responsible for the adherence of the toxin to the cell surface while the N-terminus mediates transport of the light chain from the endocytic vesicle to the cytosol. After translocation, the light chain (L) hydrolyzes the 197-Gln-|-Arg-198 bond in SNAP-25, thereby blocking neurotransmitter release. Inhibition of acetylcholine release results in flaccid paralysis, with frequent heart or respiratory failure. [[http://www.uniprot.org/uniprot/SNP25_HUMAN SNP25_HUMAN]] t-SNARE involved in the molecular regulation of neurotransmitter release. May play an important role in the synaptic function of specific neuronal systems. Associates with proteins involved in vesicle docking and membrane fusion. Regulates plasma membrane recycling through its interaction with CENPF.  
[https://www.uniprot.org/uniprot/BXA1_CLOBH BXA1_CLOBH] Inhibits acetylcholine release. The botulinum toxin binds with high affinity to peripheral neuronal presynaptic membrane to the secretory vesicle protein SV2. It binds directly to the largest luminal loop of SV2A, SV2B and SV2C. It is then internalized by receptor-mediated endocytosis. The C-terminus of the heavy chain (H) is responsible for the adherence of the toxin to the cell surface while the N-terminus mediates transport of the light chain from the endocytic vesicle to the cytosol. After translocation, the light chain (L) hydrolyzes the 197-Gln-|-Arg-198 bond in SNAP-25, thereby blocking neurotransmitter release. Inhibition of acetylcholine release results in flaccid paralysis, with frequent heart or respiratory failure.
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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   <jmolCheckbox>
   <jmolCheckbox>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/dd/3dda_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/dd/3dda_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
   </jmolCheckbox>
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==See Also==
==See Also==
*[[Botulinum neurotoxin|Botulinum neurotoxin]]
*[[Botulinum neurotoxin 3D structures|Botulinum neurotoxin 3D structures]]
*[[Synaptosomal-associated protein|Synaptosomal-associated protein]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Bacillus botulinus van ermengem 1896]]
[[Category: Clostridium botulinum]]
[[Category: Bontoxilysin]]
[[Category: Large Structures]]
[[Category: Kumaran, D]]
[[Category: Synthetic construct]]
[[Category: Swaminathan, S]]
[[Category: Kumaran D]]
[[Category: Alternative splicing]]
[[Category: Swaminathan S]]
[[Category: Bio-warfare agent]]
[[Category: Botox]]
[[Category: Botulinum neurotoxin type some]]
[[Category: Catalytic domain]]
[[Category: Cell junction]]
[[Category: Coiled coil]]
[[Category: Endopeptidase]]
[[Category: Enzyme-substrate complex]]
[[Category: Hydrolase]]
[[Category: Lipoprotein]]
[[Category: Metal-binding]]
[[Category: Metalloprotease]]
[[Category: Palmitate]]
[[Category: Pharmaceutical]]
[[Category: Phosphoprotein]]
[[Category: Protease]]
[[Category: Secreted]]
[[Category: Synapse]]
[[Category: Synaptosome]]
[[Category: Syntaxin]]
[[Category: Transmembrane]]
[[Category: Zinc]]

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