Structure-Based Inhibitors Exhibit Differential Activities against Helicobacter pylori and Escherichia coli Undecaprenyl Pyrophosphate Synthases

Figure 3

Computer virtual screening of the H. pylori UPPS inhibitors. Two compounds, BTB06061 shown in (a) and HTS04781 in (b), were identified from the computer fitting of the Maybridge compounds into the active site of E. coli and H. pylori UPPS. The data of enzyme activities in the presence of different concentrations of the inhibitors were used to determine the IC₅₀ values of the inhibitors. The compounds displayed IC₅₀ of 350 and 363 μM, respectively, in inhibiting H. pylori UPPS activity. However, the IC₅₀ of BTB06061 became 71 μM in inhibiting E. coli UPPS and HTS04781 was almost inactive against the enzyme. The modeled structures of the inhibitor bound in the active site of H. pylori UPPS are shown at the bottom.

(a)

(b)