View source for 3zuq


==Crystal structure of an engineered botulinum neurotoxin type B - derivative, LC-B-GS-Hn-B==
<StructureSection load='3zuq' size='340' side='right'caption='[[3zuq]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3zuq]] 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=3ZUQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZUQ 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]] 2.7&#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=3zuq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zuq OCA], [https://pdbe.org/3zuq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zuq RCSB], [https://www.ebi.ac.uk/pdbsum/3zuq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zuq ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/BXB_CLOBO BXB_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 that cleaves the '76-Gln-|-Phe-77' bond of synaptobrevin-2.
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== Publication Abstract from PubMed ==
Targeted secretion inhibitors (TSIs) are a new class of engineered biopharmaceutical molecules derived from the botulinum neurotoxins (BoNTs). They consist of the metalloprotease light chain (LC) and translocation domain (Hn) of BoNT; they thus lack the native toxicity towards motor neurons but are able to target soluble N-ethylmaleimide-sensitive fusion protein attachment receptor (SNARE) proteins. These functional fragment (LHn) derivatives are expressed as single-chain proteins and require post-translational activation into di-chain molecules for function. A range of BoNT derivatives have been produced to demonstrate the successful use of engineered SNARE substrate peptides at the LC-Hn interface that gives these molecules self-activating capabilities. Alternatively, recognition sites for specific exoproteases can be engineered to allow controlled activation. Here, the crystal structures of three LHn derivatives are reported between 2.7 and 3.0 A resolution. Two of these molecules are derivatives of serotype A that contain a SNARE peptide. Additionally, a third structure corresponds to LHn serotype B that includes peptide linkers at the exoprotease activation site. In all three cases the added engineered segments could not be modelled owing to disorder. However, these structures highlight the strong interactions holding the LHn fold together despite the inclusion of significant polypeptide sequences at the LC-Hn interface.

Structures of engineered Clostridium botulinum neurotoxin derivatives.,Masuyer G, Stancombe P, Chaddock JA, Acharya KR Acta Crystallogr Sect F Struct Biol Cryst Commun. 2011 Dec 1;67(Pt 12):1466-72., Epub 2011 Nov 25. PMID:22139146<ref>PMID:22139146</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 3zuq" style="background-color:#fffaf0;"></div>

==See Also==
*[[Botulinum neurotoxin 3D structures|Botulinum neurotoxin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Clostridium botulinum]]
[[Category: Large Structures]]
[[Category: Acharya KR]]
[[Category: Chaddock JA]]
[[Category: Masuyer G]]
[[Category: Stancombe P]]