Insights into the molecular interactions between urease subunit gamma from MRSA and drugs: .

, an important human pathogen, is developing resistance against a wide range of antibiotics. The antibiotic resistance in has created the need to identify new drug targets, and to develop new drugs candidates. In the current study, urease subunit gamma from Methicillin Resistant (MRSA 252) was studied as a potential drug target, through protein-ligand interactions. Urease is the main virulence factor of MRSA, it catalyzes the conversion of urea into ammonia that is required for the survival of bacteria during acid stress. Its subunits and accessory proteins can serve as targets for drug discovery and development. Present study describes the cloning, expression, and purification of urease subunit gamma from MRSA 252. This was followed by screening of 100 US-FDA approved drugs against this protein using STD-NMR spectroscopy and among them, 15 drugs showed significant STD effects. studies predicted that these drugs interacted mainly non-covalent interactions, such as hydrogen bond, aromatic hydrogen bonding, π-π stacking, π-cation interactions, salt bridges, and halogen bonding. The thermal stability of UreA in the presence of these interacting drugs was evaluated using differential scanning fluorimetry (DSF), which revealed a significant effect on the of UreA. Additionally, the inhibitory effects of these drugs on urease activity were assessed using a urease inhibition assay with Jack bean urease. The results showed that these drugs possess enzyme inhibitory activity, potentially impacting the survival of . These hits need further biochemical and mechanistic studies to validate their therapeutic potential against the MRSA infections.