6bvd: Difference between revisions
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==Structure of Botulinum Neurotoxin Serotype HA Light Chain== | |||
<StructureSection load='6bvd' size='340' side='right'caption='[[6bvd]], [[Resolution|resolution]] 2.09Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6bvd]] 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=6BVD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BVD 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]] 2.09Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <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=6bvd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bvd OCA], [https://pdbe.org/6bvd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bvd RCSB], [https://www.ebi.ac.uk/pdbsum/6bvd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bvd ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/A0A384E125_CLOBO A0A384E125_CLOBO] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The extreme toxicity of botulinum neurotoxins (BoNTs) relies on their specific cleavage of SNARE proteins, which eventually leads to muscle paralysis. One newly identified mosaic toxin, BoNT/HA (aka H or FA), cleaves VAMP-2 at a unique position between residues L54 and E55, but the molecular basis underlying VAMP-2-recognition of BoNT/HA remains poorly characterized. Here, we report a approximately 2.09 A resolution crystal structure of the light chain protease domain of BoNT/HA (LC/HA). Structural comparison between LC/HA and LC of BoNT/F1 (LC/F1) reveals distinctive hydrophobic and electrostatic features near the active sites, which may explain their different VAMP-2 cleavage sites. When compared to BoNT/F5 that cleaves VAMP-2 at the same site as BoNT/HA, LC/HA displays higher affinity for VAMP-2, which could be caused by their different surface charge properties surrounding a VAMP-2 exosite-binding cleft. Furthermore, systematic mutagenesis studies on VAMP-2 and structural modeling demonstrate that residues R47 to K59 spanning the cleavage site in VAMP-2 may adopt a novel extended conformation when interacting with LC/HA and LC/F5. Taken together, our structure provides new insights into substrate-recognition of BoNT/HA and paves the way for rational design of small molecule or peptide inhibitors against LC/HA. | |||
Structural and biochemical characterization of the protease domain of the mosaic botulinum neurotoxin type HA.,Lam KH, Sikorra S, Weisemann J, Maatsch H, Perry K, Rummel A, Binz T, Jin R Pathog Dis. 2018 Apr 23. pii: 4982781. doi: 10.1093/femspd/fty044. PMID:29688327<ref>PMID:29688327</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 6bvd" style="background-color:#fffaf0;"></div> | ||
[[Category: Jin | |||
==See Also== | |||
*[[Botulinum neurotoxin 3D structures|Botulinum neurotoxin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Clostridium botulinum]] | |||
[[Category: Large Structures]] | |||
[[Category: Jin R]] | |||
[[Category: Lam K]] | |||
Latest revision as of 17:51, 4 October 2023
Structure of Botulinum Neurotoxin Serotype HA Light ChainStructure of Botulinum Neurotoxin Serotype HA Light Chain
Structural highlights
FunctionPublication Abstract from PubMedThe extreme toxicity of botulinum neurotoxins (BoNTs) relies on their specific cleavage of SNARE proteins, which eventually leads to muscle paralysis. One newly identified mosaic toxin, BoNT/HA (aka H or FA), cleaves VAMP-2 at a unique position between residues L54 and E55, but the molecular basis underlying VAMP-2-recognition of BoNT/HA remains poorly characterized. Here, we report a approximately 2.09 A resolution crystal structure of the light chain protease domain of BoNT/HA (LC/HA). Structural comparison between LC/HA and LC of BoNT/F1 (LC/F1) reveals distinctive hydrophobic and electrostatic features near the active sites, which may explain their different VAMP-2 cleavage sites. When compared to BoNT/F5 that cleaves VAMP-2 at the same site as BoNT/HA, LC/HA displays higher affinity for VAMP-2, which could be caused by their different surface charge properties surrounding a VAMP-2 exosite-binding cleft. Furthermore, systematic mutagenesis studies on VAMP-2 and structural modeling demonstrate that residues R47 to K59 spanning the cleavage site in VAMP-2 may adopt a novel extended conformation when interacting with LC/HA and LC/F5. Taken together, our structure provides new insights into substrate-recognition of BoNT/HA and paves the way for rational design of small molecule or peptide inhibitors against LC/HA. Structural and biochemical characterization of the protease domain of the mosaic botulinum neurotoxin type HA.,Lam KH, Sikorra S, Weisemann J, Maatsch H, Perry K, Rummel A, Binz T, Jin R Pathog Dis. 2018 Apr 23. pii: 4982781. doi: 10.1093/femspd/fty044. PMID:29688327[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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