View source for 8bvd


==FimH lectin domain in complex with mannose C-linked to quinoline==
<StructureSection load='8bvd' size='340' side='right'caption='[[8bvd]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8bvd]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_UTI89 Escherichia coli UTI89]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8BVD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BVD 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]] 2.995&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RLO:(2~{R},3~{S},4~{R},5~{S},6~{R})-2-(hydroxymethyl)-6-[(~{E})-3-quinolin-6-ylprop-2-enyl]oxane-3,4,5-triol'>RLO</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=8bvd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8bvd OCA], [https://pdbe.org/8bvd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8bvd RCSB], [https://www.ebi.ac.uk/pdbsum/8bvd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8bvd ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/FIMH_ECOLI FIMH_ECOLI] Involved in regulation of length and mediation of adhesion of type 1 fimbriae (but not necessary for the production of fimbriae). Adhesin responsible for the binding to D-mannose. It is laterally positioned at intervals in the structure of the type 1 fimbriae. In order to integrate FimH in the fimbriae FimF and FimG are needed.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Selective antiadhesion antagonists of Uropathogenic Escherichia coli (UPEC) type-1 Fimbrial adhesin (FimH) are attractive alternatives for antibiotic therapies and prophylaxes against acute or recurrent urinary tract infections (UTIs) caused by UPECs. A rational small library of FimH antagonists based on previously described C-linked allyl alpha-D-mannopyranoside was synthesized using Heck cross-coupling reaction using a series of iodoaryl derivatives. This work reports two new members of FimH antagonist amongst the above family with sub nanomolar affinity. The resulting hydrophobic aglycones, including constrained alkene and aryl groups, were designed to provide additional favorable binding interactions with the so-called FimH "tyrosine gate". The newly synthesized C-linked glycomimetic antagonists, having a hydrolytically stable anomeric linkage, exhibited improved binding when compared to previously published analogs, as demonstrated by affinity measurement through interactions by FimH lectin. The crystal structure of FimH co-crystallized with one of the nanomolar antagonists revealed the binding mode of this inhibitor into the active site of the tyrosine gate. In addition, selected mannopyranoside constructs neither affected bacterial growth or cell viability nor interfered with antibiotic activity. C-linked mannoside antagonists were effective in decreasing bacterial adhesion to human bladder epithelial cells (HTB-9). Therefore, these molecules constituted additional therapeutic candidates' worth further development in the search for potent anti-adhesive drugs against infections caused by UPEC.

Insightful Improvement in the Design of Potent Uropathogenic E. coli FimH Antagonists.,Mousavifar L, Sarshar M, Bridot C, Scribano D, Ambrosi C, Palamara AT, Vergoten G, Roubinet B, Landemarre L, Bouckaert J, Roy R Pharmaceutics. 2023 Feb 4;15(2):527. doi: 10.3390/pharmaceutics15020527. PMID:36839848<ref>PMID:36839848</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8bvd" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Escherichia coli UTI89]]
[[Category: Large Structures]]
[[Category: Bouckaert J]]
[[Category: Bridot C]]