title: Bacterial cell wall. MurJ is the flippase of lipid-linked precursors for peptidoglycan biogenesis.
abstract: Peptidoglycan (PG) is a polysaccharide matrix that protects bacteria from osmotic lysis. Inhibition of its biogenesis is a proven strategy for killing bacteria with antibiotics. The assembly of PG requires disaccharide-pentapeptide building blocks attached to a polyisoprene lipid carrier called lipid II. Although the stages of lipid II synthesis are known, the identity of the essential flippase that translocates it across the cytoplasmic membrane for PG polymerization is unclear. We developed an assay for lipid II flippase activity and used a chemical genetic strategy to rapidly and specifically block flippase function. We combined these approaches to demonstrate that MurJ is the lipid II flippase in Escherichia coli.
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Lok-To
authors.initials: LT
authors.lastname: Sham
authors.affiliation: Department of Microbiology, Ohio State University, Columbus, OH 43210, USA.
authors.forename: Emily K
authors.initials: EK
authors.lastname: Butler
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Lebar
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Kahne
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA. thomas_bernhardt@hms.harvard.edu ruiz.82@osu.edu.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Bernhardt
authors.affiliation: Department of Microbiology, Ohio State University, Columbus, OH 43210, USA. thomas_bernhardt@hms.harvard.edu ruiz.82@osu.edu.
authors.forename: Natividad
authors.initials: N
authors.lastname: Ruiz
mesh_terms: D002473:Cell Wall / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*; D008698:Mesylates / Q000494:pharmacology; D008958:Models, Molecular; D010457:Peptidoglycan / Q000096:biosynthesis* / Q000737:chemistry; D049294:Phospholipid Transfer Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*; D011487:Protein Conformation; D014538:Uridine Diphosphate N-Acetylmuramic Acid / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D029968:Escherichia coli Proteins; D008698:Mesylates; C584574:MurJ protein, E coli; D010457:Peptidoglycan; D049294:Phospholipid Transfer Proteins; D014538:Uridine Diphosphate N-Acetylmuramic Acid; C069249:muramyl-NAc-(pentapeptide)pyrophosphoryl-undecaprenol; C109153:(2-sulfonatoethyl)methanethiosulfonate