6Z6C

Crystal structurel of FleA lectin in complex with a monovalent inhibitor

This is a non-PDB format compatible entry.

Summary for 6Z6C

• Entry DOI: 10.2210/pdb6z6c/pdb
• Descriptor: Fucose-specific lectin, 4-((1-(2-(2-(2-(2-hydroxyethoxy)ethoxy)ethoxy)ethyl)-1H-1,2,3-triazol-4-yl)methoxy)benzyl-a-L-thiofucoside, GLYCEROL, ... (6 entities in total)
• Functional Keywords: lectin, antiadhesive, fucose binding, sugar binding protein
• Biological source: Aspergillus fumigatus Af293
• Total number of polymer chains: 2
• Total formula weight: 74865.34

Authors

Varrot, A. (deposition date: 2020-05-28, release date: 2021-04-07, Last modification date: 2024-01-24)

Primary citation

Dussouy, C.,Lalys, P.A.,Cabanettes, A.,Lehot, V.,Deniaud, D.,Gillon, E.,Balloy, V.,Varrot, A.,Gouin, S.G.
Hexavalent thiofucosides to probe the role of the Aspergillus fumigatus lectin FleA in fungal pathogenicity.
Org.Biomol.Chem., 19:3234-3240, 2021

PubMed Abstract: 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 (K = 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.

PubMed: 33885578
DOI: 10.1039/d1ob00152c

Experimental method

X-RAY DIFFRACTION (1.4 Å)