X-ray structure of Streptococcus pneumoniae PBP2x, a primary penicillin target enzyme

Nat Struct Biol. 1996 Mar;3(3):284-9. doi: 10.1038/nsb0396-284.


All beta-lactam antibiotics exert their biological effects by interacting with a unique class of proteins, the penicillin-binding proteins (PBPs). These membrane proteins are involved in the biosynthesis of the murein or peptidoglycan, a mesh-like structure which completely surrounds the bacterial cell. Sequence similarities indicate that one domain of these proteins belongs to a large family of beta-lactam-recognizing proteins, which includes the active-site serine beta-lactamases. We here report the first three-dimensional crystal structure of a high molecular weight penicillin-binding protein, PBP2x of Streptococcus pneumoniae, at 3.5 A resolution. The molecule has three domains, the central domain being a transpeptidase, which is a suitable target for antibiotic development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins*
  • Binding Sites
  • Carrier Proteins / chemistry*
  • Cell Membrane / enzymology
  • Cell Membrane / ultrastructure
  • Crystallography, X-Ray
  • Hexosyltransferases*
  • Membrane Proteins / chemistry
  • Methionine
  • Models, Molecular
  • Models, Structural
  • Molecular Sequence Data
  • Muramoylpentapeptide Carboxypeptidase / chemistry*
  • Penicillin-Binding Proteins
  • Penicillins / metabolism
  • Peptidyl Transferases*
  • Protein Conformation*
  • Protein Structure, Secondary
  • Streptococcus pneumoniae / enzymology*


  • Bacterial Proteins
  • Carrier Proteins
  • Membrane Proteins
  • Penicillin-Binding Proteins
  • Penicillins
  • Methionine
  • Peptidyl Transferases
  • Hexosyltransferases
  • Muramoylpentapeptide Carboxypeptidase

Associated data

  • PDB/1PMD