6f4e: Difference between revisions
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<StructureSection load='6f4e' size='340' side='right' caption='[[6f4e]], [[Resolution|resolution]] 2.40Å' scene=''> | <StructureSection load='6f4e' size='340' side='right' caption='[[6f4e]], [[Resolution|resolution]] 2.40Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6f4e]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6F4E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6F4E FirstGlance]. <br> | <table><tr><td colspan='2'>[[6f4e]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_botulinus"_van_ermengem_1896 "bacillus botulinus" van ermengem 1896]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6F4E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6F4E FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6f47|6f47]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6f47|6f47]]</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=6f4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6f4e OCA], [http://pdbe.org/6f4e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6f4e RCSB], [http://www.ebi.ac.uk/pdbsum/6f4e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6f4e ProSAT]</span></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=6f4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6f4e OCA], [http://pdbe.org/6f4e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6f4e RCSB], [http://www.ebi.ac.uk/pdbsum/6f4e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6f4e ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Botulinum neurotoxins (BoNTs) are among the most potent toxins known and are also used to treat an increasing number of medical disorders. There are seven well-established serotypes (BoNT/A-G), which all act as zinc-dependent endopeptidases targeting specific members of the SNARE proteins required for synaptic vesicle exocytosis in neurons. A new toxin serotype, BoNT/X, was recently identified. It cleaves not only the canonical targets, vesicle associated membrane proteins (VAMP) 1/2/3 at a unique site, but also has the unique ability to cleave VAMP4/5 and Ykt6. Here we report the 1.35 A X-ray crystal structure of the light chain of BoNT/X (LC/X). LC/X shares the core fold common to all other BoNTs, demonstrating that LC/X is a bona fide member of BoNT-LCs. We found that access to the catalytic pocket of LC/X is more restricted, and the regions lining the catalytic pocket are not conserved compared to other BoNTs. Kinetic studies revealed that LC/X cleaves VAMP1 with a ten times higher efficiency than BoNT/B and the tetanus neurotoxin. The structural information provides a molecular basis to understand the convergence/divergence between BoNT/X and other BoNTs, to develop effective LC inhibitors, and to engineer new scientific tools and therapeutic toxins targeting distinct SNARE proteins in cells. | |||
Structural characterisation of the catalytic domain of botulinum neurotoxin X - high activity and unique substrate specificity.,Masuyer G, Zhang S, Barkho S, Shen Y, Henriksson L, Kosenina S, Dong M, Stenmark P Sci Rep. 2018 Mar 14;8(1):4518. doi: 10.1038/s41598-018-22842-4. PMID:29540745<ref>PMID:29540745</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6f4e" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Bacillus botulinus van ermengem 1896]] | |||
[[Category: Barkho, S]] | [[Category: Barkho, S]] | ||
[[Category: Dong, M]] | [[Category: Dong, M]] | ||
Latest revision as of 10:20, 28 March 2018
Crystal structure of the zinc-free catalytic domain of botulinum neurotoxin XCrystal structure of the zinc-free catalytic domain of botulinum neurotoxin X
Structural highlights
Publication Abstract from PubMedBotulinum neurotoxins (BoNTs) are among the most potent toxins known and are also used to treat an increasing number of medical disorders. There are seven well-established serotypes (BoNT/A-G), which all act as zinc-dependent endopeptidases targeting specific members of the SNARE proteins required for synaptic vesicle exocytosis in neurons. A new toxin serotype, BoNT/X, was recently identified. It cleaves not only the canonical targets, vesicle associated membrane proteins (VAMP) 1/2/3 at a unique site, but also has the unique ability to cleave VAMP4/5 and Ykt6. Here we report the 1.35 A X-ray crystal structure of the light chain of BoNT/X (LC/X). LC/X shares the core fold common to all other BoNTs, demonstrating that LC/X is a bona fide member of BoNT-LCs. We found that access to the catalytic pocket of LC/X is more restricted, and the regions lining the catalytic pocket are not conserved compared to other BoNTs. Kinetic studies revealed that LC/X cleaves VAMP1 with a ten times higher efficiency than BoNT/B and the tetanus neurotoxin. The structural information provides a molecular basis to understand the convergence/divergence between BoNT/X and other BoNTs, to develop effective LC inhibitors, and to engineer new scientific tools and therapeutic toxins targeting distinct SNARE proteins in cells. Structural characterisation of the catalytic domain of botulinum neurotoxin X - high activity and unique substrate specificity.,Masuyer G, Zhang S, Barkho S, Shen Y, Henriksson L, Kosenina S, Dong M, Stenmark P Sci Rep. 2018 Mar 14;8(1):4518. doi: 10.1038/s41598-018-22842-4. PMID:29540745[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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