Bacterial Transferase MraY, a Source of Inspiration towards New Antibiotics

Curr Med Chem. 2018;25(42):6013-6029. doi: 10.2174/0929867325666180330095154.

Abstract

The bacterial resistance to antibiotics constitutes more than ever a severe public health problem. The enzymes involved in bacterial peptidoglycan biosynthesis are pertinent targets for developing new antibiotics, notably the MraY transferase that is not targeted by any marketed drug. Many research groups are currently working on the study or the inhibition of this enzyme. After a concise overview of the role, mechanism and inhibition of MraY, the structure-activity relationships of 5'-triazole-containing aminoribosyluridine inhibitors, we previously synthetized, will be presented. The recently published MraY X-ray structures allowed us to achieve a molecular virtual high-throughput screening of commercial databases and our in-house library resulting in the identification of promising compounds for the further development of new antibiotics.

Keywords: MraY; biological evaluations; docking; molecular modelling; mutagenesis; nucleoside antibiotics; triazoles..

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / metabolism
  • Anti-Bacterial Agents / pharmacology
  • Bacteria / enzymology
  • Bacteria / metabolism*
  • Bacterial Proteins / antagonists & inhibitors*
  • Bacterial Proteins / metabolism
  • Binding Sites
  • Drug Design
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / pharmacology
  • Molecular Docking Simulation
  • Peptidoglycan / metabolism
  • Structure-Activity Relationship
  • Transferases (Other Substituted Phosphate Groups)
  • Transferases / antagonists & inhibitors*
  • Transferases / metabolism
  • Triazoles / chemistry
  • Triazoles / metabolism

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Enzyme Inhibitors
  • Peptidoglycan
  • Triazoles
  • Transferases
  • Transferases (Other Substituted Phosphate Groups)
  • mraY protein, Bacteria