Dipeptidyl peptidase 11 (PgDPP11); A Target Enabling Package

Porphyromonas gingivalis (P. gingivalis) is the main causative agent of Periodontitis, the most widespread inflammatory condition world-wide. Recently this organism has been implicated in several systemic conditions, such as Alzheimer’s disease and type 2 diabetes. P. gingivalis does not ferment carbohydrates, instead it uses proteases to generate energy and carbon source. Dipeptidyl peptidase 11 plays a central role in the energy metabolism of this bacterium and has been proposed as an attractive drug target. This TEP provide early tools to develop inhibitors of PgDPP11, including purification protocols of recombinant proteins, a crystal structure of the protein in complex with a dipeptide, crystallisation conditions suitable for crystallography-based fragment screening, an inhibition assay and fragment hits in the active site and an allosteric site. These molecules provide a promising starting point for the development of more specific and potent PgDPP11 inhibitors.