title: X-ray structure of Streptococcus pneumoniae PBP2x, a primary penicillin target enzyme.
abstract: 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.
authors.affiliation: Institut de Biologie Structurale, Laboratoire de Cristallographie Macromoléculaire, Grenoble, France.
authors.forename: S
authors.initials: S
authors.lastname: Pares
authors.forename: N
authors.initials: N
authors.lastname: Mouz
authors.forename: Y
authors.initials: Y
authors.lastname: Pétillot
authors.forename: R
authors.initials: R
authors.lastname: Hakenbeck
authors.forename: O
authors.initials: O
authors.lastname: Dideberg
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry*; D002462:Cell Membrane / Q000201:enzymology / Q000648:ultrastructure; D018360:Crystallography, X-Ray; D006602:Hexosyltransferases; D008565:Membrane Proteins / Q000737:chemistry; D008715:Methionine; D008958:Models, Molecular; D008961:Models, Structural; D008969:Molecular Sequence Data; D002267:Muramoylpentapeptide Carboxypeptidase / Q000737:chemistry*; D046915:Penicillin-Binding Proteins; D010406:Penicillins / Q000378:metabolism; D010458:Peptidyl Transferases; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D013296:Streptococcus pneumoniae / Q000201:enzymology*
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D008565:Membrane Proteins; D046915:Penicillin-Binding Proteins; D010406:Penicillins; D008715:Methionine; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase