3zl2: Difference between revisions
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==A thiazolyl-mannoside bound to FimH, orthorhombic space group== | |||
<StructureSection load='3zl2' size='340' side='right' caption='[[3zl2]], [[Resolution|resolution]] 1.25Å' scene=''> | |||
{ | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3zl2]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli_j96 Escherichia coli j96]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZL2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ZL2 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BWG:N-{5-[(1R)-1-HYDROXYETHYL]-1,3-THIAZOL-2-YL}-ALPHA-D-MANNOPYRANOSYLAMINE'>BWG</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3zl1|3zl1]]</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=3zl2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zl2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3zl2 RCSB], [http://www.ebi.ac.uk/pdbsum/3zl2 PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Adherent-invasive Escherichia coli (AIEC) have previously been shown to induce gut inflammation in patients with Crohn's disease (CD). We developed a set of mannosides to prevent AIEC attachment to the gut by blocking the FimH bacterial adhesin. The crystal structure of the FimH lectin domain in complex with a lead thiazolylaminomannoside highlighted the preferential position for pharmacomodulations. A small library of analogues showing nanomolar affinity for FimH was then developed. Notably, AIEC attachment to intestinal cells was efficiently prevented by the most active compound and at around 10000-fold and 100-fold lower concentrations than mannose and the potent FimH inhibitor heptylmannoside, respectively. An ex vivo assay performed on the colonic tissue of a transgenic mouse model of CD confirmed this antiadhesive potential. Given the key role of AIEC in the chronic intestinal inflammation of CD patients, these results suggest a potential antiadhesive treatment with the FimH inhibitors developed. | |||
Thiazolylaminomannosides As Potent Antiadhesives of Type 1 Piliated Escherichia coli Isolated from Crohn's Disease Patients.,Brument S, Sivignon A, Dumych TI, Moreau N, Roos G, Guerardel Y, Chalopin T, Deniaud D, Bilyy RO, Darfeuille-Michaud A, Bouckaert J, Gouin SG J Med Chem. 2013 Jun 24. PMID:23795713<ref>PMID:23795713</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
== | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Escherichia coli j96]] | [[Category: Escherichia coli j96]] | ||
[[Category: Bilyy, R O | [[Category: Bilyy, R O]] | ||
[[Category: Bouckaert, J | [[Category: Bouckaert, J]] | ||
[[Category: Brument, S | [[Category: Brument, S]] | ||
[[Category: Chalopin, T | [[Category: Chalopin, T]] | ||
[[Category: Darfeuille-Michaud, A | [[Category: Darfeuille-Michaud, A]] | ||
[[Category: Deniaud, D | [[Category: Deniaud, D]] | ||
[[Category: Dumych, T I | [[Category: Dumych, T I]] | ||
[[Category: Gouin, S G | [[Category: Gouin, S G]] | ||
[[Category: Guerardel, Y | [[Category: Guerardel, Y]] | ||
[[Category: Moreau, N | [[Category: Moreau, N]] | ||
[[Category: Roos, G | [[Category: Roos, G]] | ||
[[Category: Sivignon, A | [[Category: Sivignon, A]] | ||
[[Category: Cell adhesion]] | [[Category: Cell adhesion]] | ||
[[Category: Crohn's disease]] | [[Category: Crohn's disease]] | ||
