5aal: Difference between revisions
New page: '''Unreleased structure''' The entry 5aal is ON HOLD Authors: Bouckaert, J. Description: Complex of the FimH lectin with a C-linked para-biphenyl ethylene alpha-D-mannoside in soaked t... |
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==Complex of the FimH lectin with a C-linked para-biphenyl ethylene alpha-D-mannoside in soaked trigonal crystals at 2.45 A resolution== | |||
<StructureSection load='5aal' size='340' side='right'caption='[[5aal]], [[Resolution|resolution]] 2.45Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5aal]] is a 2 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=5AAL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5AAL 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]] 2.45Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8L8:(2R,3S,4R,5S,6R)-2-(HYDROXYMETHYL)-6-[(Z)-3-(4-PHENYLPHENYL)PROP-2-ENYL]OXANE-3,4,5-TRIOL'>8L8</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=5aal FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5aal OCA], [https://pdbe.org/5aal PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5aal RCSB], [https://www.ebi.ac.uk/pdbsum/5aal PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5aal ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q1R2J4_ECOUT Q1R2J4_ECOUT] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Selective inhibitors of the type 1 fimbrial adhesin FimH are recognized as attractive alternatives for antibiotic therapies and prophylaxes against Escherichia coli infections such as urinary-tract infections. To construct these inhibitors, the alpha-d-mannopyranoside of high-mannose N-glycans, recognized with exclusive specificity on glycoprotein receptors by FimH, forms the basal structure. A hydrophobic aglycon is then linked to the mannose by the O1 oxygen inherently present in the alpha-anomeric configuration. Substitution of this O atom by a carbon introduces a C-glycosidic bond, which may enhance the therapeutic potential of such compounds owing to the inability of enzymes to degrade C-glycosidic bonds. Here, the first crystal structures of the E. coli FimH adhesin in complex with C-glycosidically linked mannopyranosides are presented. These findings explain the role of the spacer in positioning biphenyl ligands for interactions by means of aromatic stacking in the tyrosine gate of FimH and how the normally hydrated C-glycosidic link is tolerated. As these new compounds can bind FimH, it can be assumed that they have the potential to serve as potent new antagonists of FimH, paving the way for the design of a new family of anti-adhesive compounds against urinary-tract infections. | |||
Structures of C-mannosylated anti-adhesives bound to the type 1 fimbrial FimH adhesin.,de Ruyck J, Lensink MF, Bouckaert J IUCrJ. 2016 Feb 26;3(Pt 3):163-7. doi: 10.1107/S2052252516002487. eCollection, 2016 May 1. PMID:27158502<ref>PMID:27158502</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Bouckaert | <div class="pdbe-citations 5aal" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Adhesin 3D structures|Adhesin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Escherichia coli UTI89]] | |||
[[Category: Large Structures]] | |||
[[Category: Bouckaert J]] | |||
[[Category: De Ruyck J]] | |||
Latest revision as of 14:06, 10 January 2024
Complex of the FimH lectin with a C-linked para-biphenyl ethylene alpha-D-mannoside in soaked trigonal crystals at 2.45 A resolutionComplex of the FimH lectin with a C-linked para-biphenyl ethylene alpha-D-mannoside in soaked trigonal crystals at 2.45 A resolution
Structural highlights
FunctionPublication Abstract from PubMedSelective inhibitors of the type 1 fimbrial adhesin FimH are recognized as attractive alternatives for antibiotic therapies and prophylaxes against Escherichia coli infections such as urinary-tract infections. To construct these inhibitors, the alpha-d-mannopyranoside of high-mannose N-glycans, recognized with exclusive specificity on glycoprotein receptors by FimH, forms the basal structure. A hydrophobic aglycon is then linked to the mannose by the O1 oxygen inherently present in the alpha-anomeric configuration. Substitution of this O atom by a carbon introduces a C-glycosidic bond, which may enhance the therapeutic potential of such compounds owing to the inability of enzymes to degrade C-glycosidic bonds. Here, the first crystal structures of the E. coli FimH adhesin in complex with C-glycosidically linked mannopyranosides are presented. These findings explain the role of the spacer in positioning biphenyl ligands for interactions by means of aromatic stacking in the tyrosine gate of FimH and how the normally hydrated C-glycosidic link is tolerated. As these new compounds can bind FimH, it can be assumed that they have the potential to serve as potent new antagonists of FimH, paving the way for the design of a new family of anti-adhesive compounds against urinary-tract infections. Structures of C-mannosylated anti-adhesives bound to the type 1 fimbrial FimH adhesin.,de Ruyck J, Lensink MF, Bouckaert J IUCrJ. 2016 Feb 26;3(Pt 3):163-7. doi: 10.1107/S2052252516002487. eCollection, 2016 May 1. PMID:27158502[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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