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| | <StructureSection load='2vxr' size='340' side='right'caption='[[2vxr]], [[Resolution|resolution]] 1.90Å' scene=''> | | <StructureSection load='2vxr' size='340' side='right'caption='[[2vxr]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2vxr]] is a 1 chain structure with sequence from [https://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=2VXR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VXR FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2vxr]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridium_botulinum Clostridium botulinum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VXR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VXR FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.9Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1zb7|1zb7]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=2vxr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vxr OCA], [https://pdbe.org/2vxr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vxr RCSB], [https://www.ebi.ac.uk/pdbsum/2vxr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vxr ProSAT]</span></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=2vxr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vxr OCA], [https://pdbe.org/2vxr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vxr RCSB], [https://www.ebi.ac.uk/pdbsum/2vxr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vxr ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/BXG_CLOBO BXG_CLOBO] Botulinum toxin acts by inhibiting neurotransmitter release. It binds to peripheral neuronal synapses, is internalized and moves by retrograde transport up the axon into the spinal cord where it can move between postsynaptic and presynaptic neurons. It inhibits neurotransmitter release by acting as a zinc endopeptidase. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bacillus botulinus van ermengem 1896]] | + | [[Category: Clostridium botulinum]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Dupuy, J]] | + | [[Category: Dupuy J]] |
| - | [[Category: Stenmark, P]] | + | [[Category: Stenmark P]] |
| - | [[Category: Stevens, R C]] | + | [[Category: Stevens RC]] |
| - | [[Category: Binding domain]]
| + | |
| - | [[Category: Botulinum]]
| + | |
| - | [[Category: Ganglioside]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Metalloprotease]]
| + | |
| - | [[Category: Neurotoxin]]
| + | |
| - | [[Category: Protease]]
| + | |
| - | [[Category: Receptor]]
| + | |
| - | [[Category: Secreted]]
| + | |
| - | [[Category: Toxin]]
| + | |
| Structural highlights
Function
BXG_CLOBO Botulinum toxin acts by inhibiting neurotransmitter release. It binds to peripheral neuronal synapses, is internalized and moves by retrograde transport up the axon into the spinal cord where it can move between postsynaptic and presynaptic neurons. It inhibits neurotransmitter release by acting as a zinc endopeptidase.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Botulinum neurotoxins (BoNTs) typically bind the neuronal cell surface via dual interactions with both protein receptors and gangliosides. We present here the 1.9-A X-ray structure of the BoNT serotype G (BoNT/G) receptor binding domain (residues 868-1297) and a detailed view of protein receptor and ganglioside binding regions. The ganglioside binding motif (SxWY) has a conserved structure compared to the corresponding regions in BoNT serotype A and BoNT serotype B (BoNT/B), but several features of interactions with the hydrophilic face of the ganglioside are absent at the opposite side of the motif in the BoNT/G ganglioside binding cleft. This may significantly reduce the affinity between BoNT/G and gangliosides. BoNT/G and BoNT/B share the protein receptor synaptotagmin (Syt) I/II. The Syt binding site has a conserved hydrophobic plateau located centrally in the proposed protein receptor binding interface (Tyr1189, Phe1202, Ala1204, Pro1205, and Phe1212). Interestingly, only 5 of 14 residues that are important for binding between Syt-II and BoNT/B are conserved in BoNT/G, suggesting that the means by which BoNT/G and BoNT/B bind Syt diverges more than previously appreciated. Indeed, substitution of Syt-II Phe47 and Phe55 with alanine residues had little effect on the binding of BoNT/G, but strongly reduced the binding of BoNT/B. Furthermore, an extended solvent-exposed hydrophobic loop, located between the Syt binding site and the ganglioside binding cleft, may serve as a third membrane association and binding element to contribute to high-affinity binding to the neuronal membrane. While BoNT/G and BoNT/B are homologous to each other and both utilize Syt-I/Syt-II as their protein receptor, the precise means by which these two toxin serotypes bind to Syt appears surprisingly divergent.
Crystal structure of the botulinum neurotoxin type G binding domain: insight into cell surface binding.,Stenmark P, Dong M, Dupuy J, Chapman ER, Stevens RC J Mol Biol. 2010 Apr 16;397(5):1287-97. Epub 2010 Feb 26. PMID:20219474[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Stenmark P, Dong M, Dupuy J, Chapman ER, Stevens RC. Crystal structure of the botulinum neurotoxin type G binding domain: insight into cell surface binding. J Mol Biol. 2010 Apr 16;397(5):1287-97. Epub 2010 Feb 26. PMID:20219474 doi:10.1016/j.jmb.2010.02.041
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