Progress in the search for histidine acid phosphatase inhibitors in Francisella tularensis
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Histidine acid phosphatase (hap) is an important enzyme in the bacteria Francisella Tularensis that is responsible for the cleavage of phosphate groups from phosphorylated proteins. Here, we report on the process for discovering potential inhibitors of the hap enzyme. A sample of the active enzyme was obtained through cloning of the DNA sequence and expression and purification of the enzyme. Using the GOLD program, virtual screening was performed on a crystal structure of the hap enzyme found in the Protein Database (PDB) and two compounds from the top results were ordered from ChemBridge. Three compounds, the two found from virtual screening and a third random compound, were tested for inhibition using a spectrophotometric assay. Out of the three compounds, only compound 5852635 showed potential inhibition of the hap enzyme after enzyme inhibition assays. Further work can now be done on compound 5852635 to determine whether it will consistently inhibit the hap enzyme and the IC50 of this compound. Also, more virtual screening work can be done to find other compounds which inhibit the hap enzyme.