Identification of Novel Inhibitors Against Glutamate Racemase of Klebsiella Pneumoniae Through Homology Modeling and Docking Studies

Abstract

Abstract Klebsiella pneumoniae is a bacterium that gives rise to infections in humans as well as animals. It is found in the environment, including in soil and water, and can also be present in the human microbiome, particularly in the gastrointestinal tract. Klebsiella pneumoniae can lead to a range of illnesses, including pneumonia, infections of the urinary tract, and wound infections. It is more typically found in patients with compromised immune systems, such as those who are hospitalized, have underlying medical conditions, or are taking certain medications that suppress the immune system. Antibiotic-resistant strains of Klebsiella pneumoniae, such as those that are resistant to carbapenem antibiotics, have become a significant public health concern in recent years. These strains can be difficult to treat and can lead to severe infections and high mortality rates. MurI is an enzyme found in the bacterial species Klebsiella pneumoniae that is implicated in the production of peptidoglycan, a key component of the bacterial cell wall. Inhibiting the activity of MurI has been shown to be an effective technique to establish new antibiotics for the treatment of infections caused by K. pneumoniae. In this study, we used homology modeling and docking techniques to identify novel inhibitors of MurI. Homology modeling is a computational method that uses the structure of a similar protein to predict the structure of a target protein. Docking is a method that predicts how well a small molecule will fit into the active site of a protein. To identify potential inhibitors of MurI, we first built a homology model of the enzyme using the structure of a related protein as a template. We then used this model to perform docking studies with a large database of small molecules. The docking results allowed us to identify several compounds that had good binding affinity for the active site of MurI. We then performed further experiments to confirm the inhibitory activity of these compounds against MurI in vitro. Overall, our study demonstrates the utility of homology modeling and docking in the identification of novel inhibitors of MurI. These compounds may have the ability as new antibiotics for the treatment of Klebsiella pneumoniae infections.