Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 102, Issue 3, Pages 577-582Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0407186102
Keywords
antibiotic; cell wall; transpeptidase; glycosyltransferase
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Bacterial cell division is a complex, multimolecular process that requires biosynthesis of new pepticloglycan by penicillin-binding proteins (PBPs) during cell wall elongation and septum formation steps. Streptococcus pneumoniae has three bifunctional (class A) PBPs that catalyze both polymerization of glycan chains (glycosyl-transfer) and cross-linking of pentapepticlic bridges (transpeptidation) during the pepticloglycan biosynthetic process. In addition to playing important roles in cell division, PBPs are also the targets for)beta-lactam antibiotics and thus play key roles in drug-resistance mechanisms. The crystal structure of a soluble form of pneumococcal PBP1b (PBPlb*) has been solved to 1.9 A, thus providing previously unclescribed structural information regarding a class A PBP from any organism. PBP1b* is a three-domain molecule harboring a short peptide from the glycosyltransferase domain bound to an interdomain linker region, the transpepticlase domain, and a C-terminal region. The structure of PBP1b* complexed with beta-lactam antibiotics reveals that ligand recognition requires a conformational modification involving conserved elements within the cleft. The open and closed structures of PBP1b* suggest how class A PBPs may become activated as novel pepticloglycan synthesis becomes necessary during the cell division process. In addition, this structure provides an initial framework for the understanding of the role of class A PBPs in the development of antibiotic resistance.
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