View source for 7ayn


==Crystal structure of the lectin domain of the FimH variant Arg98Ala, in complex with Methyl 3-chloro-4-D-mannopyranosyloxy-3-biphenylcarboxylate==
<StructureSection load='7ayn' size='340' side='right'caption='[[7ayn]], [[Resolution|resolution]] 1.42&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7ayn]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AYN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AYN 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]] 1.42&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SBQ:methyl+3-[3-chloranyl-4-[(2~{R},3~{S},4~{S},5~{S},6~{R})-6-(hydroxymethyl)-3,4,5-tris(oxidanyl)oxan-2-yl]oxy-phenyl]benzoate'>SBQ</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=7ayn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ayn OCA], [https://pdbe.org/7ayn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ayn RCSB], [https://www.ebi.ac.uk/pdbsum/7ayn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ayn 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 ==
Bacterial resistance has become an important challenge in the treatment of urinary tract infections. The underlying resistance mechanisms can most likely be circumvented with an antiadhesive approach, antagonizing the lectin FimH located at the tip of fimbriae of uropathogenic E. coli. Here we report on a novel series of FimH antagonists based on the 1-(alpha-d-mannopyranosyl)-4-phenyl-1,2,3-triazole scaffold, designed to incorporate carboxylic acid or ester functions to interact with FimH Arg98. The most potent representative of the series, ester 11e, displayed a Kd value of 7.6 nM for the lectin domain of FimH with a general conclusion that all esters outperform carboxylates in terms of affinity. Surprisingly, all compounds from this new series exhibited improved binding affinities also for the R98A mutant, indicating another possible interaction contributing to binding. Our study on 1-(alpha-d-mannopyranosyl)-4-phenyl-1,2,3-triazole-based FimH antagonists offers proof that targeting Arg98 side chain by a "chemical common sense", i.e. by introduction of the acidic moiety to form ionic bond with Arg98 is most likely unsuitable approach to boost FimH antagonists' potency.

Does targeting Arg98 of FimH lead to high affinity antagonists?,Tomasic T, Rabbani S, Jakob RP, Reisner A, Jakopin Z, Maier T, Ernst B, Anderluh M Eur J Med Chem. 2020 Dec 9;211:113093. doi: 10.1016/j.ejmech.2020.113093. PMID:33340913<ref>PMID:33340913</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7ayn" style="background-color:#fffaf0;"></div>

==See Also==
*[[Adhesin 3D structures|Adhesin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli K-12]]
[[Category: Large Structures]]
[[Category: Anderluh M]]
[[Category: Ernst B]]
[[Category: Jakob RP]]
[[Category: Jakopin Z]]
[[Category: Maier T]]
[[Category: Rabbani S]]
[[Category: Reisner A]]
[[Category: Tomasic T]]