7olw

Structure of the N-terminal domain of BC2L-C lectin (1-131) in complex with a synthetic beta-N-fucoside ligand

spinqualitylabelsall models 7olw, resolution 1.32Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7olw is a 1 chain structure with sequence from Burkholderia cenocepacia J2315. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.32Å Ligands: VJW Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function B4EH86_BURCJ 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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