6hmw: Difference between revisions
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<StructureSection load='6hmw' size='340' side='right'caption='[[6hmw]], [[Resolution|resolution]] 1.95Å' scene=''> | <StructureSection load='6hmw' size='340' side='right'caption='[[6hmw]], [[Resolution|resolution]] 1.95Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6hmw]] is a 10 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HMW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HMW FirstGlance]. <br> | <table><tr><td colspan='2'>[[6hmw]] is a 10 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillo_virgola_del_koch"_trevisan_1884 "bacillo virgola del koch" trevisan 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HMW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HMW FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BCN:BICINE'>BCN</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FUL:BETA-L-FUCOSE'>FUL</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BCN:BICINE'>BCN</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FUL:BETA-L-FUCOSE'>FUL</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6hjd|6hjd]], [[5elb|5elb]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6hjd|6hjd]], [[5elb|5elb]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ctxB, C9J66_18955, EN12_07055, ERS013165_03981, ERS013197_06217, ERS013202_03762, ERS013206_03003 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=666 "Bacillo virgola del Koch" Trevisan 1884])</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=6hmw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hmw OCA], [http://pdbe.org/6hmw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hmw RCSB], [http://www.ebi.ac.uk/pdbsum/6hmw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hmw 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=6hmw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hmw OCA], [http://pdbe.org/6hmw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hmw RCSB], [http://www.ebi.ac.uk/pdbsum/6hmw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hmw ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Cholera is a life-threatening diarrhoeal disease caused by the human pathogen Vibrio cholerae. Infection occurs after ingestion of the bacteria, which colonize the human small intestine and secrete their major virulence factor - the cholera toxin (CT). The GM1 ganglioside is considered the primary receptor of the CT, but recent studies suggest that also fucosylated receptors such as histo-blood group antigens are important for cellular uptake and toxicity. Recently, a special focus has been on the histo-blood group antigen Lewis(x) (Le(x)), however, where and how the CT binds to Le(x) remains unclear. Here we report the high-resolution crystal structure (1.5 A) of the receptor-binding B-subunits of the CT bound to the Le(x) trisaccharide, and complementary quantitative binding data for CT holotoxins. Le(x), and also L-fucose alone, bind to the secondary binding site of the toxin, distinct from the GM1 binding site. In contrast, fucosyl-GM1 mainly binds to the primary binding site due to high-affinity interactions of its GM1 core. Le(x) is the first histo-blood group antigen of non-secretor phenotype structurally investigated in complex with CT. Together with the quantitative binding data, this allows unique insight into why individuals with non-secretor phenotype are more prone to severe cholera than so-called 'secretors'. | |||
Crystal structures of cholera toxin in complex with fucosylated receptors point to importance of secondary binding site.,Heim JB, Hodnik V, Heggelund JE, Anderluh G, Krengel U Sci Rep. 2019 Aug 22;9(1):12243. doi: 10.1038/s41598-019-48579-2. PMID:31439922<ref>PMID:31439922</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6hmw" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Bacillo virgola del koch trevisan 1884]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Heim, J B]] | [[Category: Heim, J B]] | ||
Revision as of 14:06, 2 October 2019
Cholera toxin classical B-pentamer in complex with fucoseCholera toxin classical B-pentamer in complex with fucose
Structural highlights
Publication Abstract from PubMedCholera is a life-threatening diarrhoeal disease caused by the human pathogen Vibrio cholerae. Infection occurs after ingestion of the bacteria, which colonize the human small intestine and secrete their major virulence factor - the cholera toxin (CT). The GM1 ganglioside is considered the primary receptor of the CT, but recent studies suggest that also fucosylated receptors such as histo-blood group antigens are important for cellular uptake and toxicity. Recently, a special focus has been on the histo-blood group antigen Lewis(x) (Le(x)), however, where and how the CT binds to Le(x) remains unclear. Here we report the high-resolution crystal structure (1.5 A) of the receptor-binding B-subunits of the CT bound to the Le(x) trisaccharide, and complementary quantitative binding data for CT holotoxins. Le(x), and also L-fucose alone, bind to the secondary binding site of the toxin, distinct from the GM1 binding site. In contrast, fucosyl-GM1 mainly binds to the primary binding site due to high-affinity interactions of its GM1 core. Le(x) is the first histo-blood group antigen of non-secretor phenotype structurally investigated in complex with CT. Together with the quantitative binding data, this allows unique insight into why individuals with non-secretor phenotype are more prone to severe cholera than so-called 'secretors'. Crystal structures of cholera toxin in complex with fucosylated receptors point to importance of secondary binding site.,Heim JB, Hodnik V, Heggelund JE, Anderluh G, Krengel U Sci Rep. 2019 Aug 22;9(1):12243. doi: 10.1038/s41598-019-48579-2. PMID:31439922[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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