An allosteric pocket for inhibition of bacterial Enzyme I identified by NMR-based fragment screening.

ABSTRACT: Enzyme I (EI), which is the key enzyme to activate the bacterial phosphotransferase system, plays an important role in the regulation of several metabolic pathways and controls the biology of bacterial cells at multiple levels. The conservation and ubiquity of EI among different types of bacteria makes the enzyme a potential target for antimicrobial research. Here, we use NMR-based fragment screening to identify novel inhibitors of EI. We identify three molecular fragments that allosterically inhibit the phosphoryl transfer reaction catalyzed by EI by interacting with the enzyme at a surface pocket located more than 10 Å away from the substrate binding site. Interestingly, although the three molecules share the same binding pocket, we observe that two of the discovered EI ligands act as co

SUBMITTER: Nguyen TT 

PROVIDER: S-EPMC7385036 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature