View source for 6zvm


==Botulinum neurotoxin B2 binding domain in complex with GD1a==
<StructureSection load='6zvm' size='340' side='right'caption='[[6zvm]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6zvm]] 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=6ZVM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZVM FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=GAL:BETA-D-GALACTOSE'>GAL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NGA:N-ACETYL-D-GALACTOSAMINE'>NGA</scene>, <scene name='pdbligand=SIA:O-SIALIC+ACID'>SIA</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=6zvm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zvm OCA], [https://pdbe.org/6zvm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zvm RCSB], [https://www.ebi.ac.uk/pdbsum/6zvm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zvm ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q8GR96_CLOBO Q8GR96_CLOBO] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Botulinum neurotoxins (BoNTs) can be used therapeutically to treat a wide range of neuromuscular and neurological conditions. A collection of natural BoNT variants exists which can be classified into serologically distinct serotypes (BoNT/B), and further divided into subtypes (BoNT/B1, B2, ...). BoNT subtypes share a high degree of sequence identity within the same serotype yet can display large variation in toxicity. One such example is BoNT/B2, which was isolated from Clostridium botulinum strain 111 in a clinical case of botulism, and presents a 10-fold lower toxicity than BoNT/B1. In an effort to understand the molecular mechanisms behind this difference in potency, we here present the crystal structures of BoNT/B2 in complex with the ganglioside receptor GD1a, and with the human synaptotagmin I protein receptor. We show, using receptor-binding assays, that BoNT/B2 has a slightly higher affinity for GD1a than BoNT/B1, and confirm its considerably weaker affinity for its protein receptors. Although the overall receptor-binding mechanism is conserved for both receptors, structural analysis suggests the lower affinity of BoNT/B2 is the result of key substitutions, where hydrophobic interactions important for synaptotagmin-binding are replaced by polar residues. This study provides a template to drive the development of future BoNT therapeutic molecules centered on assessing the natural subtype variations in receptor-binding that appears to be one of the principal stages driving toxicity.

Structural and Biochemical Characterization of Botulinum Neurotoxin Subtype B2 Binding to Its Receptors.,Davies JR, Masuyer G, Stenmark P Toxins (Basel). 2020 Sep 17;12(9). pii: toxins12090603. doi:, 10.3390/toxins12090603. PMID:32957706<ref>PMID:32957706</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6zvm" style="background-color:#fffaf0;"></div>

==See Also==
*[[Botulinum neurotoxin 3D structures|Botulinum neurotoxin 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Clostridium botulinum]]
[[Category: Large Structures]]
[[Category: Davies JR]]
[[Category: Masuyer G]]
[[Category: Stenmark P]]