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| | ==Crystal structure of HA17-HA33-Lactulose== | | ==Crystal structure of HA17-HA33-Lactulose== |
| - | <StructureSection load='5bqu' size='340' side='right' caption='[[5bqu]], [[Resolution|resolution]] 2.38Å' scene=''> | + | <StructureSection load='5bqu' size='340' side='right'caption='[[5bqu]], [[Resolution|resolution]] 2.38Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5bqu]] is a 3 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=5BQU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5BQU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5bqu]] is a 3 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=5BQU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5BQU FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FRU:FRUCTOSE'>FRU</scene>, <scene name='pdbligand=GAL:BETA-D-GALACTOSE'>GAL</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.38Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4lo1|4lo1]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FRU:FRUCTOSE'>FRU</scene>, <scene name='pdbligand=GAL:BETA-D-GALACTOSE'>GAL</scene>, <scene name='pdbligand=PRD_900038:lactulose'>PRD_900038</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HA-33, ha33, ha34 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1491 "Bacillus botulinus" van Ermengem 1896]), ha17, HA-17 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1491 "Bacillus botulinus" van Ermengem 1896])</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=5bqu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bqu OCA], [https://pdbe.org/5bqu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5bqu RCSB], [https://www.ebi.ac.uk/pdbsum/5bqu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5bqu 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=5bqu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bqu OCA], [http://pdbe.org/5bqu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5bqu RCSB], [http://www.ebi.ac.uk/pdbsum/5bqu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5bqu ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/Q45878_CLOBO Q45878_CLOBO] |
| - | Botulinum neurotoxins (BoNTs) cause the disease botulism manifested by flaccid paralysis that could be fatal to humans and animals. Oral ingestion of the toxin with contaminated food is one of the most common routes for botulism. BoNT assembles with several auxiliary proteins to survive in the gastrointestinal tract and is subsequently transported through the intestinal epithelium into the general circulation. Several hemagglutinin proteins form a multi-protein complex (HA complex) that recognizes host glycans on the intestinal epithelial cell surface to facilitate BoNT absorption. Blocking carbohydrate binding to the HA complex could significantly inhibit the oral toxicity of BoNT. Here, we identify lactulose, a galactose-containing non-digestible sugar commonly used to treat constipation, as a prototype inhibitor against oral BoNT/A intoxication. As revealed by a crystal structure, lactulose binds to the HA complex at the same site where the host galactose-containing carbohydrate receptors bind. In vitro assays using intestinal Caco-2 cells demonstrated that lactulose inhibits HA from compromising the integrity of the epithelial cell monolayers and blocks the internalization of HA. Furthermore, co-administration of lactulose significantly protected mice against BoNT/A oral intoxication in vivo. Taken together, these data encourage the development of carbohydrate receptor mimics as a therapeutic intervention to prevent BoNT oral intoxication.
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| - | Inhibiting oral intoxication of botulinum neurotoxin A complex by carbohydrate receptor mimics.,Lee K, Lam KH, Kruel AM, Mahrhold S, Perry K, Cheng LW, Rummel A, Jin R Toxicon. 2015 Aug 10. pii: S0041-0101(15)30033-7. doi:, 10.1016/j.toxicon.2015.08.003. PMID:26272706<ref>PMID:26272706</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 5bqu" style="background-color:#fffaf0;"></div>
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| - | == References ==
| + | |
| - | <references/>
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bacillus botulinus van ermengem 1896]] | + | [[Category: Clostridium botulinum]] |
| - | [[Category: Jin, R]] | + | [[Category: Large Structures]] |
| - | [[Category: Lam, K]] | + | [[Category: Jin R]] |
| - | [[Category: Lee, K]] | + | [[Category: Lam K]] |
| - | [[Category: Botulinum neurotoxin some]] | + | [[Category: Lee K]] |
| - | [[Category: Hemagglutinin]]
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| - | [[Category: Iptg]]
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| - | [[Category: Protein binding]]
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