Crystal structure of MraY, an essential membrane enzyme for bacterial cell wall synthesis

Science. 2013 Aug 30;341(6149):1012-1016. doi: 10.1126/science.1236501.

Abstract

MraY (phospho-MurNAc-pentapeptide translocase) is an integral membrane enzyme that catalyzes an essential step of bacterial cell wall biosynthesis: the transfer of the peptidoglycan precursor phospho-MurNAc-pentapeptide to the lipid carrier undecaprenyl phosphate. MraY has long been considered a promising target for the development of antibiotics, but the lack of a structure has hindered mechanistic understanding of this critical enzyme and the enzyme superfamily in general. The superfamily includes enzymes involved in bacterial lipopolysaccharide/teichoic acid formation and eukaryotic N-linked glycosylation, modifications that are central in many biological processes. We present the crystal structure of MraY from Aquifex aeolicus (MraYAA) at 3.3 Å resolution, which allows us to visualize the overall architecture, locate Mg(2+) within the active site, and provide a structural basis of catalysis for this class of enzyme.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacteria / enzymology*
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Catalytic Domain
  • Cell Wall / chemistry*
  • Cell Wall / enzymology
  • Crystallography, X-Ray
  • Cytoplasm / enzymology
  • Membrane Proteins / chemistry*
  • Membrane Proteins / genetics
  • Periplasm / enzymology
  • Protein Conformation
  • Protein Structure, Secondary
  • Transferases (Other Substituted Phosphate Groups)
  • Transferases / chemistry*
  • Transferases / genetics

Substances

  • Bacterial Proteins
  • Membrane Proteins
  • Transferases
  • Transferases (Other Substituted Phosphate Groups)
  • mraY protein, Bacteria

Associated data

  • PDB/4J72