title: Penicillin-binding proteins of gram-negative bacteria.
abstract: beta-Lactam antibiotics exert their antibacterial effects by inactivating the high-molecular-weight penicillin-binding proteins (PBPs) that are responsible for the final stages of peptidoglycan biosynthesis. The availability of the amino acid sequences of several low-molecular-weight PBPs, high-molecular-weight PBPs, and active-site serine beta-lactamases has provided evidence that these groups of enzymes have a common, but distant, evolutionary origin. This view is strongly supported by the recent finding of a similarity in the three-dimensional structures of a low-molecular-weight PBP and class A beta-lactamases. The high-molecular-weight PBPs of Escherichia coli are believed to possess an amino-terminal peptidoglycan transglycosylase domain and a carboxy-terminal penicillin-sensitive transpeptidase domain. These enzymes are inserted in the cytoplasmic membrane only at their amino termini, and water-soluble forms have been obtained that should be suitable for crystallization and X-ray analysis. Resistance to beta-lactam antibiotics mediated by alterations of PBPs has been reported in some gram-negative bacteria. In isolates of Neisseria gonorrhoeae with chromosomally mediated resistance, penicillin-resistant PBPs have arisen from the introduction of multiple amino acid substitutions within the transpeptidase domain of the enzymes.
authors.affiliation: Microbial Genetics Group, School of Biological Sciences, University of Sussex, Brighton, United Kingdom.
authors.forename: B G
authors.initials: BG
authors.lastname: Spratt
authors.forename: K D
authors.initials: KD
authors.lastname: Cromie
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000032:analysis / Q000502:physiology*; D006090:Gram-Negative Bacteria / Q000378:metabolism*; D006602:Hexosyltransferases; D008969:Molecular Sequence Data; D002267:Muramoylpentapeptide Carboxypeptidase / Q000032:analysis / Q000502:physiology*; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases; D011487:Protein Conformation; D001618:beta-Lactamases / Q000032:analysis
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D001618:beta-Lactamases