Inhibition of tobramycin resistant protein aminoglycoside nucleotidyl transferase using geneticin as inhibitor

Aminoglycosides are broad-spectrum antimicrobial agents, however, effectiveness of these antibiotics is reduced due to modifications carried out by enzymes, which reduces affinity of the drug for the target ribosome. In Gram-negative pathogens, the most common aminoglycoside resistance enzymes is aminoglycoside nucleotidyl transferase, which offers resistance to gentamicin, tobramycin, and kanamycin. Generated 3-D model Molecular docking study of aminoglycoside nucleotidyl transferase protein with tobramycin and inhibitor such as G418 (also known as Geneticin) revealed similar binding pocket as per experimental findings of tobramycin. The residues HIS42, ASP44, TYR74, GLU88, ALA100 and TYR134 of aminoglycoside nucleotidyl transferase interacts with inhibitor. Thus, these studies could be useful to understand tobramycin resistance mechanism due to the aminoglycoside nucleotidyl transferase. A three-dimensional structure of aminoglycoside nucleotidyl transferase was constructed using homology modelling technique. Its reliability was checked with the help of different online programs.