5lzg
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 5lzg is ON HOLD Authors: Heggelund, J.E., Martinsen, T., Krengel, U. Description: Cholera toxin El Tor B-pentamer in complex with inhibitor PC262 [...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Cholera toxin El Tor B-pentamer in complex with inhibitor PC262== | |
| + | <StructureSection load='5lzg' size='340' side='right'caption='[[5lzg]], [[Resolution|resolution]] 1.13Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5lzg]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Vibrio_cholerae_O1_biovar_El_Tor_str._N16961 Vibrio cholerae O1 biovar El Tor str. N16961]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LZG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5LZG 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]] 1.13Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7BN:(2~{R},4~{S},5~{R},6~{R})-5-acetamido-2-[4-[3-[2-[(2~{S},3~{R},4~{R},5~{R},6~{R})-6-(hydroxymethyl)-3,4,5-tris(oxidanyl)oxan-2-yl]ethylamino]-3-oxidanylidene-propyl]-1,2,3-triazol-1-yl]-4-oxidanyl-6-[(1~{R},2~{R})-1,2,3-tris(oxidanyl)propyl]oxane-2-carboxylic+acid'>7BN</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=MRD:(4R)-2-METHYLPENTANE-2,4-DIOL'>MRD</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</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=5lzg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lzg OCA], [https://pdbe.org/5lzg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5lzg RCSB], [https://www.ebi.ac.uk/pdbsum/5lzg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5lzg ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/CHTB_VIBCH CHTB_VIBCH] The B subunit pentameric ring directs the A subunit to its target by binding to the GM1 gangliosides present on the surface of the intestinal epithelial cells. It can bind five GM1 gangliosides. It has no toxic activity by itself. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Cholera is a life-threatening disease in many countries, and new drugs are clearly needed. C-glycosidic antagonists may serve such a purpose. Here we report atomic-resolution crystal structures of three such compounds in complexes with the cholera toxin. The structures give unprecedented atomic details of the molecular interactions and show how the inhibitors efficiently block the GM1 binding site. These molecules are well suited for development into low-cost prophylactic drugs, due to their relatively easy synthesis and their resistance to glycolytic enzymes. One of the compounds links two toxin B-pentamers in the crystal structure, which may yield improved inhibition through the formation of toxin aggregates. These structures can spark the improved design of GM1 mimics, either alone or as multivalent inhibitors connecting multiple GM1-binding sites. Future developments may further include compounds that link the primary and secondary binding sites. Serving as decoys, receptor mimics may lessen symptoms while avoiding the use of antibiotics. | ||
| - | + | Towards new cholera prophylactics and treatment: Crystal structures of bacterial enterotoxins in complex with GM1 mimics.,Heggelund JE, Mackenzie A, Martinsen T, Heim JB, Cheshev P, Bernardi A, Krengel U Sci Rep. 2017 May 24;7(1):2326. doi: 10.1038/s41598-017-02179-0. PMID:28539625<ref>PMID:28539625</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 5lzg" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | == References == |
| - | [[Category: Krengel | + | <references/> |
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Vibrio cholerae O1 biovar El Tor str. N16961]] | ||
| + | [[Category: Heggelund JE]] | ||
| + | [[Category: Krengel U]] | ||
| + | [[Category: Martinsen T]] | ||
Current revision
Cholera toxin El Tor B-pentamer in complex with inhibitor PC262
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