View source for 7olu


==Structure of the N-terminal domain of BC2L-C lectin (1-131) in complex with a synthetic beta-C-fucoside ligand==
<StructureSection load='7olu' size='340' side='right'caption='[[7olu]], [[Resolution|resolution]] 1.79&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7olu]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Burkholderia_cenocepacia_J2315 Burkholderia cenocepacia J2315]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OLU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OLU 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]] 1.793&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=VJT:(2-(4-(beta-L-fucopyranosylethynyl)phenyl)-2-methylpropan-1-amine'>VJT</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=7olu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7olu OCA], [https://pdbe.org/7olu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7olu RCSB], [https://www.ebi.ac.uk/pdbsum/7olu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7olu ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/B4EH86_BURCJ B4EH86_BURCJ] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Multidrug-resistant pathogens such as Burkholderia cenocepacia have become a hazard in the context of healthcare-associated infections, especially for patients admitted with cystic fibrosis or immuno-compromising conditions. Like other opportunistic Gram-negative bacteria, this pathogen establishes virulence and biofilms through lectin-mediated adhesion. In particular, the superlectin BC2L-C is believed to cross-link human epithelial cells to B. cenocepacia during pulmonary infections. We aimed to obtain glycomimetic antagonists able to inhibit the interaction between the N-terminal domain of BC2L-C (BC2L-C-Nt) and its target fucosylated human oligosaccharides. In a previous study, we identified by fragment virtual screening and validated a small set of molecular fragments that bind BC2L-C-Nt in the vicinity of the fucose binding site. Here, we report the rational design and synthesis of bifunctional C- or N-fucosides, generated by connecting these fragments to a fucoside core using a panel of rationally selected linkers. A modular route starting from two key fucoside intermediates was implemented for the synthesis, followed by evaluation of the new compounds as BC2L-C-Nt ligands with a range of techniques (surface plasmon resonance, isothermal titration calorimetry, saturation transfer difference NMR, differential scanning calorimetry, and X-ray crystallography). This study resulted in a hit molecule with an order of magnitude gain over the starting methyl fucoside and in two crystal structures of antagonist/lectin complexes.

Targeting a Multidrug-Resistant Pathogen: First Generation Antagonists of Burkholderia cenocepacia's BC2L-C Lectin.,Bermeo R, Lal K, Ruggeri D, Lanaro D, Mazzotta S, Vasile F, Imberty A, Belvisi L, Varrot A, Bernardi A ACS Chem Biol. 2022 Oct 21;17(10):2899-2910. doi: 10.1021/acschembio.2c00532. , Epub 2022 Sep 29. PMID:36174276<ref>PMID:36174276</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7olu" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Burkholderia cenocepacia J2315]]
[[Category: Large Structures]]
[[Category: Bermeo R]]
[[Category: Varrot A]]