Fig. 1.

Fragment screening pipeline. Scheme of the experimental protocol employed for discovery of novel inhibitors of EI. A library of 1,000 molecular fragments is screened against EI by STD and CSP NMR experiments. The affinity of 30 positive hits for the enzyme is characterized by NMR titration experiments. 6 low-millimolar ligands are tested for their ability to inhibit the phosphoryl-transfer reaction catalyzed by the enzyme, resulting in discovery of 3 allosteric inhibitors of EI.