6z6c | pdb_00006z6c

Crystal structurel of FleA lectin in complex with a monovalent inhibitor

spinqualitylabelsall models 6z6c, resolution 1.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6z6c is a 2 chain structure with sequence from Aspergillus fumigatus Af293. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.4Å Ligands: GOL, NA, PGE, Q9Q Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function LECF_ASPFU Multispecific lectin that is able to recognize L-fucose in all possible linkages (PubMed:23695231, PubMed:27058347, PubMed:24340081, PubMed:25760594). These could be found not only in decomposed plant matter in soil, which is the natural environment for A.fumigatus, but also in various epitopes on human tissues (PubMed:25760594). Mediates binding of A.fumigatus conidia to airway mucinin a fucose dependent manner (PubMed:27058347). Stimulates IL-8 production by human bronchial cells in a dose-dependent manner, contributing to the inflammatory response observed upon the exposure of a patient to A.fumigatus, and thus might be an important virulence factor involved in an early stage of A.fumigatus infection (PubMed:24340081). Publication Abstract from PubMed Aspergillus fumigatus is a pathogenic fungus infecting the respiratory system and responsible for a variety of life-threatening lung diseases. A fucose-binding lectin named FleA which has a controversial role in A. fumigatus pathogenesis was recently identified. New chemical probes with high affinity and enzymatic stability are needed to explore the role of FleA in the infection process. In this study, we developed potent FleA antagonists based on optimized and non-hydrolysable thiofucoside ligands. We first synthesized a set of monovalent sugars showing micromolar affinity for FleA by isothermal titration calorimetry. The most potent derivative was co-crystallized with FleA to gain insights into the binding mode in operation. Its chemical multimerization on a cyclodextrin scaffold led to an hexavalent compound with a significantly enhanced binding affinity (Kd = 223 +/- 21 nM) thanks to a chelate binding mode. The compound could probe the role of bronchial epithelial cells in a FleA-mediated response to tissue invasion. Hexavalent thiofucosides to probe the role of the Aspergillus fumigatus lectin FleA in fungal pathogenicity.,Dussouy C, Lalys PA, Cabanettes A, Lehot V, Deniaud D, Gillon E, Balloy V, Varrot A, Gouin SG Org Biomol Chem. 2021 Apr 14;19(14):3234-3240. doi: 10.1039/d1ob00152c. Epub 2021, Mar 24. PMID:33885578 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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