Design of an inhibitor of Helicobacter pylori cholesteryl-α-glucoside transferase critical for bacterial colonization.

Background: Fifty percent of the world's population surves as a host for Helicobacter pylori, gastric cancer causing bacteria, that colonizes the gastric region of digestive tract. It has a remarkable capacity to infect the host stomach for the entire lifetime despite an activated host immune response.

Methods: In this study, we have performed the virtual screening analysis of protein-inhibitor binding between the glycosyl transferase enzymes of Helicobacter pylori (CapJ or HP0421) and a corresponding library of inhibitors in the known substrate-binding pockets. We have docked our library of ligands consisting of cholesterol backbone with CapJ protein and identified several ligands' interacting amino acid residues present in active site pocket(s) of the protein.

Results: In most of the cases, the ligands showed an interaction with the residues of the same pocket of the enzyme. Top three (03) hits were filtered out from the whole data set, which might act as potent inhibitors of the enzyme-substrate reaction.

Conclusions: This study describes a new possibility by which colonization of H. pylori can be limited. The reported evidence suggests that comprehensive knowledge and wet laboratory validation of these inhibitors are needed in order to develop them as lead molecules.