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Druggable allosteric sites in β‐propeller lectins

Abstract : Carbohydrate-binding proteins (lectins) are auspicious targets to combat antimicrobial resistance; however, its noncarbohydrate drug-like inhibitors are still spacious. Here, we present a druggable pocket in a β-propeller lectin BambL from Burkholderia ambifaria as a potential target for allosteric inhibitors. This site was identified employing 19F NMR fragment screening and a computational pocket prediction algorithm SiteMap. The structure-activity relationship study revealed the most promising fragment with a dissociation constant of 0.3±0.1 mM and a ligand efficiency of 0.3 kcal mol-1HA-1, which affected the orthosteric site. This effect was substantiated by site-directed mutagenesis in the orthosteric and secondary pockets. Future drug-discovery campaigns that aim to develop small molecule inhibitors can benefit from allosteric sites in lectins as a new therapeutic approach against antibiotic-resistant pathogens
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Submitted on : Wednesday, November 3, 2021 - 9:47:20 AM
Last modification on : Friday, April 1, 2022 - 3:55:37 AM


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Elena Shanina, Sakonwan Kuhaudomlarp, Kanhaya Lal, Peter Seeberger, Anne Imberty, et al.. Druggable allosteric sites in β‐propeller lectins. Angewandte Chemie International Edition, Wiley-VCH Verlag, 2021, ⟨10.1002/anie.202109339⟩. ⟨hal-03412507⟩



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