Natural Products at Work: Structural Insights into Inhibition of the Bacterial Membrane Protein MraY

Angew Chem Int Ed Engl. 2016 Sep 19;55(39):11722-4. doi: 10.1002/anie.201606396. Epub 2016 Aug 11.

Abstract

Natural(ly) fit: The X-ray crystal structure of the bacterial membrane protein MraY in complex with its natural product inhibitor muraymycin D2 is discussed. MraY catalyzes one of the membrane-associated steps in peptidoglycan biosynthesis and, therefore, represents a promising target for novel antibiotics. Structural insights derived from the protein-inhibitor complex might now pave the way for the development of new antimicrobial drugs.

Keywords: antibiotics; medicinal chemistry; natural products; peptidoglycans; protein crystallography.

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Bacteria / chemistry
  • Bacteria / drug effects
  • Bacteria / enzymology*
  • Bacteria / metabolism
  • Bacterial Infections / drug therapy
  • Bacterial Infections / microbiology
  • Bacterial Proteins / antagonists & inhibitors*
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism
  • Biological Products / chemistry
  • Biological Products / pharmacology*
  • Crystallography, X-Ray
  • Humans
  • Molecular Docking Simulation
  • Nucleosides / chemistry
  • Nucleosides / pharmacology*
  • Peptides / chemistry
  • Peptides / pharmacology*
  • Peptidoglycan / metabolism
  • Transferases (Other Substituted Phosphate Groups)
  • Transferases / antagonists & inhibitors*
  • Transferases / chemistry
  • Transferases / metabolism

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Biological Products
  • Nucleosides
  • Peptides
  • Peptidoglycan
  • muraymycin D2
  • Transferases
  • Transferases (Other Substituted Phosphate Groups)
  • mraY protein, Bacteria