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CEntre de Recherches sur les MAcromolécules Végétales |  |
Journal articles
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
https://hal.archives-ouvertes.fr/hal-03412507
Contributor : Anne Imberty Connect in order to contact the contributor
Submitted on : Wednesday, November 3, 2021 - 9:47:20 AM
Last modification on : Thursday, December 2, 2021 - 2:14:02 PM
Contributor : Anne Imberty Connect in order to contact the contributor
Submitted on : Wednesday, November 3, 2021 - 9:47:20 AM
Last modification on : Thursday, December 2, 2021 - 2:14:02 PM
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