6uc6
From Proteopedia
(Difference between revisions)
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<StructureSection load='6uc6' size='340' side='right'caption='[[6uc6]], [[Resolution|resolution]] 2.32Å' scene=''> | <StructureSection load='6uc6' size='340' side='right'caption='[[6uc6]], [[Resolution|resolution]] 2.32Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6uc6]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UC6 OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[6uc6]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridium_botulinum Clostridium botulinum] and [https://en.wikipedia.org/wiki/Vicugna_pacos Vicugna pacos]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UC6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UC6 FirstGlance]. <br> |
| - | </td></tr><tr id=' | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3200588Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6uc6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uc6 OCA], [https://pdbe.org/6uc6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6uc6 RCSB], [https://www.ebi.ac.uk/pdbsum/6uc6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6uc6 ProSAT]</span></td></tr> |
</table> | </table> | ||
== Function == | == 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. |
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Botulinum neurotoxin (BoNT) is one of the most acutely lethal toxins known to humans, and effective treatment for BoNT intoxication is urgently needed. Single-domain antibodies (VHH) have been examined as a countermeasure for BoNT because of their high stability and ease of production. Here, we investigate the structures and the neutralization mechanisms for six unique VHHs targeting BoNT/A1 or BoNT/B1. These studies reveal diverse neutralizing mechanisms by which VHHs prevent host receptor binding or block transmembrane delivery of the BoNT protease domain. Guided by this knowledge, we design heterodimeric VHHs by connecting two neutralizing VHHs via a flexible spacer so they can bind simultaneously to the toxin. These bifunctional VHHs display much greater potency in a mouse co-intoxication model than similar heterodimers unable to bind simultaneously. Taken together, our studies offer insight into antibody neutralization of BoNTs and advance our ability to design multivalent anti-pathogen VHHs with improved therapeutic properties. | ||
| + | |||
| + | Structural Insights into Rational Design of Single-Domain Antibody-Based Antitoxins against Botulinum Neurotoxins.,Lam KH, Tremblay JM, Vazquez-Cintron E, Perry K, Ondeck C, Webb RP, McNutt PM, Shoemaker CB, Jin R Cell Rep. 2020 Feb 25;30(8):2526-2539.e6. doi: 10.1016/j.celrep.2020.01.107. PMID:32101733<ref>PMID:32101733</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6uc6" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Botulinum neurotoxin 3D structures|Botulinum neurotoxin 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Clostridium botulinum]] |
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Vicugna pacos]] |
| - | [[Category: | + | [[Category: Jin R]] |
| - | [[Category: | + | [[Category: Lam K]] |
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Revision as of 07:48, 11 October 2023
Crystal structure of BoNT/B receptor-binding domain in complex with VHH JLI-H11
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