Novel Bacterial Topoisomerase Inhibitors Exploit Asp83 and the Intrinsic Flexibility of the DNA Gyrase Binding Site.

ABSTRACT: DNA gyrases are enzymes that control the topology of DNA in bacteria cells. This is a vital function for bacteria. For this reason, DNA gyrases are targeted by widely used antibiotics such as quinolones. Recently, structural and biochemical investigations identified a new class of DNA gyrase inhibitors called NBTIs (i.e., novel bacterial topoisomerase inhibitors). NBTIs are particularly promising because they are active against multi-drug resistant bacteria, an alarming clinical issue. Structural data recently demonstrated that these NBTIs bind tightly to a newly identified pocket at the dimer interface of the DNA-protein complex. In the present study, we used molecular dynamics (MD) simulations and docking calculations to shed new light on the binding of NBTIs to this site. Interestingly,

SUBMITTER: Franco-Ulloa S 

PROVIDER: S-EPMC5855675 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature