Characterization of the interaction between Escherichia coli topoisomerase IV E subunit and an ATP competitive inhibitor

Biochem Biophys Res Commun. 2015 Nov 27;467(4):961-6. doi: 10.1016/j.bbrc.2015.10.036. Epub 2015 Oct 17.

Abstract

Bacterial topoisomerase IV (ParE) is essential for DNA replication and serves as an attractive target for antibacterial drug development. The X-ray structure of the N-terminal 24 kDa ParE, responsible for ATP binding has been solved. Due to the accessibility of structural information of ParE, many potent ParE inhibitors have been discovered. In this study, a pyridylurea lead molecule against ParE of Escherichia coli (eParE) was characterized with a series of biochemical and biophysical techniques. More importantly, solution NMR analysis of compound binding to eParE provides better understanding of the molecular interactions between the inhibitor and eParE.

Keywords: (19)F NMR; Antibacterial agents; Docking; Drug design; Topoisomerase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / antagonists & inhibitors
  • Adenosine Triphosphate / metabolism*
  • Amino Acid Sequence
  • Anti-Bacterial Agents / pharmacology
  • Binding, Competitive
  • DNA Topoisomerase IV / antagonists & inhibitors
  • DNA Topoisomerase IV / chemistry
  • DNA Topoisomerase IV / metabolism*
  • DNA Topoisomerase IV / pharmacology*
  • Drug Design
  • Escherichia coli / enzymology*
  • Molecular Sequence Data
  • Nuclear Magnetic Resonance, Biomolecular

Substances

  • Anti-Bacterial Agents
  • Adenosine Triphosphate
  • DNA Topoisomerase IV