View source for 7dvl


==Crystal Structure of the Catalytic Domain of Botulinum Neurotoxin Subtype A3==
<StructureSection load='7dvl' size='340' side='right'caption='[[7dvl]], [[Resolution|resolution]] 2.01&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7dvl]] is a 2 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=7DVL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7DVL 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]] 2.006&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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=7dvl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7dvl OCA], [https://pdbe.org/7dvl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7dvl RCSB], [https://www.ebi.ac.uk/pdbsum/7dvl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7dvl ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/D3IV24_CLOBO D3IV24_CLOBO] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Botulinum neurotoxins (BoNTs) are among the most widely used therapeutic proteins; however, only two subtypes within the seven serotypes, BoNT/A1 and BoNT/B1, are currently used for medical and cosmetic applications. Distinct catalytic properties, substrate specificities, and duration of enzymatic activities potentially make other subtypes very attractive candidates to outperform conventional BoNTs in particular therapeutic applications. For example, BoNT/A3 has a significantly shorter duration of action than other BoNT/A subtypes. Notably, BoNT/A3 is the subtype with the least conserved catalytic domain among BoNT/A subtypes. This suggests that the sequence differences, many of which concern the alpha-exosite, contribute to the observed functional differences in toxin persistence by affecting the binding of the substrate SNAP-25 and/or the stability of the catalytic domain fold. To identify the molecular determinants accounting for the differences in the persistence observed for BoNT/A subtypes, we determined the crystal structure of the catalytic domain of BoNT/A3 (LC/A3). The structure of LC/A3 was found to be very similar to that of LC/A1, suggesting that the overall mode of SNAP-25 binding is common between these two proteins. However, circular dichroism (CD) thermal unfolding experiments demonstrated that LC/A3 is significantly less stable than LC/A1, implying that this might contribute to the reduced toxin persistence of BoNT/A3. These findings could be of interest in developing next generation therapeutic toxins.

Crystal structure of the catalytic domain of botulinum neurotoxin subtype A3.,Leka O, Wu Y, Li X, Kammerer RA J Biol Chem. 2021 Apr 20:100684. doi: 10.1016/j.jbc.2021.100684. PMID:33891946<ref>PMID:33891946</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7dvl" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Clostridium botulinum]]
[[Category: Large Structures]]
[[Category: Kammerer R]]
[[Category: Leka O]]
[[Category: Li X]]
[[Category: Wu Y]]