6bvd
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==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. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BVD FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6bvd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bvd OCA], [http://pdbe.org/6bvd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bvd RCSB], [http://www.ebi.ac.uk/pdbsum/6bvd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bvd ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <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> | |
| - | + | </div> | |
| + | <div class="pdbe-citations 6bvd" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Jin, R]] | [[Category: Jin, R]] | ||
[[Category: Lam, K]] | [[Category: Lam, K]] | ||
| + | [[Category: Metalloendopeptidase]] | ||
| + | [[Category: Proteolysis]] | ||
| + | [[Category: Toxin]] | ||
Revision as of 06:15, 9 May 2018
Structure of Botulinum Neurotoxin Serotype HA Light Chain
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