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==Co-crystals in the P212121 space group, of a beta-cyclodextrin spacered by triazole heptyl from alpha-D-mannose, with FimH lectin at 2.00 A resolution.== | ==Co-crystals in the P212121 space group, of a beta-cyclodextrin spacered by triazole heptyl from alpha-D-mannose, with FimH lectin at 2.00 A resolution.== | ||
<StructureSection load='6yhw' size='340' side='right'caption='[[6yhw]]' scene=''> | <StructureSection load='6yhw' size='340' side='right'caption='[[6yhw]], [[Resolution|resolution]] 1.96Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YHW OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6YHW FirstGlance]. <br> | <table><tr><td colspan='2'>[[6yhw]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=5ab1 5ab1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YHW OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6YHW FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6yhw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yhw OCA], [http://pdbe.org/6yhw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6yhw RCSB], [http://www.ebi.ac.uk/pdbsum/6yhw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6yhw ProSAT]</span></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=HP6:HEPTANE'>HP6</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=TA5:2H-1,2,3-TRIAZOL-4-YLMETHANOL'>TA5</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">fimH, fimH_1, fimH_2, fimH_3, sfaH_2, A6581_19835, ACN81_00940, AKG99_10920, AM446_24165, AM464_16260, AUQ13_11280, AWG78_008695, B6V57_25500, B9M99_24715, B9T59_08965, BON65_08035, BON69_13145, BON76_10045, BON87_19590, BvCms12BK_05011, BvCms2454_04206, C2U48_10910, C5P44_07835, C6B13_05760, CR538_22045, CRX46_08755, D2188_19245, D9G11_20470, D9H70_11375, D9I97_23340, D9J60_03345, DJ503_16470, DNQ45_27015, DS732_03965, DU321_25405, DXT73_23425, E0L12_19135, EC3234A_192c00060, ECONIH1_25860, ECTO6_04155, EIA21_01475, ELV08_23920, EQ830_16720, ERS085383_04267, F0312_06085, F1E19_12715, FNJ69_21090, FNJ83_00985, FV293_11400, FY127_19655, MS6198_50840, MS8345_04977, NCTC10090_02366, NCTC8450_00821, NCTC9045_05036, SAMEA3472056_01232, YDC107_3079 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6yhw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yhw OCA], [http://pdbe.org/6yhw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6yhw RCSB], [http://www.ebi.ac.uk/pdbsum/6yhw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6yhw ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Recently, we extended the anti-adhesive concept showing that potent FimH antagonists can block the attachment of adherent-invasive E. coli (AIEC) colonizing the intestinal mucosa of patients with Crohn's disease (CD). In this work, we designed a small library of analogs of heptylmannoside (HM), a previously identified nanomolar FimH inhibitor, but displaying poor in vivo anti-adhesive effects. The anomeric oxygen atom was replaced by a sulfur or a methylene group to prevent hydrolysis by intestinal glycosidases, and chemical groups were attached at the end of the alkyl tail. Importantly, a lead compound was shown to reduce AIEC levels in the feces, colonic and ileal mucosa after oral administration in a transgenic mouse model of CD. The compound showed a preferable low bioavailability suggesting the possibility of setting up an innovative antiadhesive therapy for CD patients in which AIEC play a key role, with the water-soluble and non-cytotoxic FimH, antagonists developed here. | |||
The anti-adhesive strategy in Crohn's disease: orally active mannosides to decolonize pathogenic Escherichia coli from the gut.,Dorta DA, Sivignon A, Chalopin T, Dumych T, Roos G, Bilyy R, Deniaud D, Krammer EM, De Ruyck J, Lensink M, Bouckaert J, Barnich N, Gouin SG Chembiochem. 2016 Mar 4. doi: 10.1002/cbic.201600018. PMID:26946458<ref>PMID:26946458</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6yhw" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Adhesin 3D structures|Adhesin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Bacillus coli migula 1895]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Bouckaert J]] | [[Category: Bouckaert, J]] | ||
[[Category: | [[Category: Ruyck, J de]] | ||
[[Category: Beta-cyclodextrin host-guest interactions inhibitor design]] | |||
[[Category: Cell adhesion]] | |||
Revision as of 09:02, 20 January 2021
Co-crystals in the P212121 space group, of a beta-cyclodextrin spacered by triazole heptyl from alpha-D-mannose, with FimH lectin at 2.00 A resolution.Co-crystals in the P212121 space group, of a beta-cyclodextrin spacered by triazole heptyl from alpha-D-mannose, with FimH lectin at 2.00 A resolution.
Structural highlights
Publication Abstract from PubMedRecently, we extended the anti-adhesive concept showing that potent FimH antagonists can block the attachment of adherent-invasive E. coli (AIEC) colonizing the intestinal mucosa of patients with Crohn's disease (CD). In this work, we designed a small library of analogs of heptylmannoside (HM), a previously identified nanomolar FimH inhibitor, but displaying poor in vivo anti-adhesive effects. The anomeric oxygen atom was replaced by a sulfur or a methylene group to prevent hydrolysis by intestinal glycosidases, and chemical groups were attached at the end of the alkyl tail. Importantly, a lead compound was shown to reduce AIEC levels in the feces, colonic and ileal mucosa after oral administration in a transgenic mouse model of CD. The compound showed a preferable low bioavailability suggesting the possibility of setting up an innovative antiadhesive therapy for CD patients in which AIEC play a key role, with the water-soluble and non-cytotoxic FimH, antagonists developed here. The anti-adhesive strategy in Crohn's disease: orally active mannosides to decolonize pathogenic Escherichia coli from the gut.,Dorta DA, Sivignon A, Chalopin T, Dumych T, Roos G, Bilyy R, Deniaud D, Krammer EM, De Ruyck J, Lensink M, Bouckaert J, Barnich N, Gouin SG Chembiochem. 2016 Mar 4. doi: 10.1002/cbic.201600018. PMID:26946458[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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