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The beast and its Achilles heel:
A novel target to fight multi-resistant pathogenic bacteria
DAC Team
Another approach of our project is the determination of the 3D structure of diadenylate cyclase (DAC) from the human pathogenic bacterium Listeria monocytogenes by crystallography. Due to the fact that the DAC from the closely related bacterium Bacillus subtilis is difficult to purify and thus to crystallize, we have decided to crystallize the DAC protein from Listeria. In addition to this, we will try to crystallize the DACs from other Gram-positive bacteria like Streptococcus and Staphylococcus .
Once having a 3D structure of a protein in hand potential inhibitor binding sites can be identified by computational modeling. Moreover, a functional DAC can be used to design a powerful in vitro screening system in order to identify potent inhibitors of the enzyme. Promising inhibitors that interfere with DAC activity could be used as a starting point for the development of drugs with improved inhibitory efficiency.
