Crystal structure of the membrane-bound bifunctional transglycosylase PBP1b from Escherichia coli

Proc Natl Acad Sci U S A. 2009 Jun 2;106(22):8824-9. doi: 10.1073/pnas.0904030106. Epub 2009 May 19.


Drug-resistant bacteria have caused serious medical problems in recent years, and the need for new antibacterial agents is undisputed. Transglycosylase, a multidomain membrane protein essential for cell wall synthesis, is an excellent target for the development of new antibiotics. Here, we determined the X-ray crystal structure of the bifunctional transglycosylase penicillin-binding protein 1b (PBP1b) from Escherichia coli in complex with its inhibitor moenomycin to 2.16-A resolution. In addition to the transglycosylase and transpeptidase domains, our structure provides a complete visualization of this important antibacterial target, and reveals a domain for protein-protein interaction and a transmembrane helix domain essential for substrate binding, enzymatic activity, and membrane orientation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Crystallography, X-Ray
  • Enzyme Inhibitors / chemistry
  • Escherichia coli / enzymology*
  • Escherichia coli Proteins / antagonists & inhibitors*
  • Escherichia coli Proteins / chemistry*
  • Molecular Sequence Data
  • Oligosaccharides / chemistry
  • Penicillin-Binding Proteins / antagonists & inhibitors*
  • Penicillin-Binding Proteins / chemistry*
  • Peptidoglycan Glycosyltransferase / antagonists & inhibitors*
  • Peptidoglycan Glycosyltransferase / chemistry*
  • Protein Conformation
  • Serine-Type D-Ala-D-Ala Carboxypeptidase / antagonists & inhibitors*
  • Serine-Type D-Ala-D-Ala Carboxypeptidase / chemistry*


  • Enzyme Inhibitors
  • Escherichia coli Proteins
  • Oligosaccharides
  • Penicillin-Binding Proteins
  • Peptidoglycan Glycosyltransferase
  • penicillin-binding protein 1B, E coli
  • Serine-Type D-Ala-D-Ala Carboxypeptidase
  • moenomycin

Associated data

  • PDB/3FWL
  • PDB/3FWM