Motion pattern of the complex involved in klebsiella pneumoniae carbapenemases and β-Lactamase inhibitor protein

Abstract:

Carbapenems, used in clinical treatment of multi-drug resistance bacterial infection, can be hydrolyzed by Klebsiella pneumoniae carbapenemases, which weaken the treatment effect of gram negative bacterial infection. It’s an important means of improving the clinical efficiency of these antibiotics to develop novel, potent and specific Klebsiella pneumoniae carbapenemase inhibitors. And β-lactamase inhibitor protein can competitively inhibits Klebsiella pneumoniae carbapenemases. The movement patterns of complex involved in Klebsiella pneumoniae carbapenemase and β-lactamase inhibitor protein are analyzed by coarse-grained models. The results indicate the movement patterns of Klebsiella pneumoniae carbapenemase change a lot after it is inhibited by β-lactamase inhibitor protein. Finally, the binding modes between the series of cyclic boronic acid β-lactamase inhibitors and Klebsiella pneumoniae carbapenemase are released by molecular docking and molecular dynamics simulation, and explained the relationship between the recognition mechanism and conformation-inhibition activity of these inhibitors from the angle of hydrogen bonds and energy. This research provides a theoretical basis of the subsequent design of the inhibitor based on the Klebsiella pneumoniae carbapenemase structure.