Druggable Allosteric Sites in β-Propeller Lectins.

ABSTRACT: Carbohydrate-binding proteins (lectins) are auspicious targets in drug discovery to combat antimicrobial resistance; however, their non-carbohydrate drug-like inhibitors are still unavailable. 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 ¹⁹ F 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^-1  HA^-1 that affected the orthosteric site. This effect was substantiated by site-directed mutagenesis in the orthosteric and secondary pockets. Futu

SUBMITTER: Shanina E 

PROVIDER: S-EPMC9298952 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature