Structural analysis of an “open” form of PBP1B from Streptococcus pneumoniae
- 1 July 2006
- journal article
- Published by Wiley in Protein Science
- Vol. 15 (7) , 1701-1709
- https://doi.org/10.1110/ps.062112106
Abstract
The class A PBP1b from Streptococcus pneumoniae is responsible for glycosyltransferase and transpeptidase (TP) reactions, forming the peptidoglycan of the bacterial cell wall. The enzyme has been produced in a stable, soluble form and undergoes time-dependent proteolysis to leave an intact TP domain. Crystals of this TP domain were obtained, diffracting to 2.2 A resolution, and the structure was solved by using molecular replacement. Analysis of the structure revealed an "open" active site, with important conformational differences to the previously determined "closed" apoenzyme. The active-site nucleophile, Ser460, is in an orientation that allows for acylation by beta-lactams. Consistent with the productive conformation of the conserved active-site catalytic residues, adjacent loops show only minor deviation from those of known acyl-enzyme structures. These findings are discussed in the context of enzyme functionality and the possible conformational sampling of PBP1b between active and inactive states.Keywords
This publication has 23 references indexed in Scilit:
- Crystal Structure of Penicillin-binding Protein 1a (PBP1a) Reveals a Mutational Hotspot Implicated in β-Lactam Resistance in Streptococcus pneumoniaeJournal of Molecular Biology, 2006
- Role of Penicillin-Binding Protein 2 (PBP2) in the Antibiotic Susceptibility and Cell Wall Cross-Linking of Staphylococcus aureus : Evidence for the Cooperative Functioning of PBP2, PBP4, and PBP2AJournal of Bacteriology, 2005
- Bacterial Resistance to β-Lactam Antibiotics: Compelling Opportunism, Compelling OpportunityChemical Reviews, 2005
- Growth and division of Streptococcus pneumoniae: localization of the high molecular weight penicillin‐binding proteins during the cell cycleMolecular Microbiology, 2003
- Probing the Catalytic Activity of a Cell Division-Specific Transpeptidase In Vivo with β-LactamsJournal of Bacteriology, 2003
- Ultrahigh Resolution Structure of a Class A β-Lactamase: On the Mechanism and Specificity of the Extended-spectrum SHV-2 EnzymeJournal of Molecular Biology, 2003
- Structural basis for the β lactam resistance of PBP2a from methicillin-resistant Staphylococcus aureusNature Structural & Molecular Biology, 2002
- Refinement of Macromolecular Structures by the Maximum-Likelihood MethodActa Crystallographica Section D-Biological Crystallography, 1997
- SWISS‐MODEL and the Swiss‐Pdb Viewer: An environment for comparative protein modelingElectrophoresis, 1997
- The CCP4 suite: programs for protein crystallographyActa Crystallographica Section D-Biological Crystallography, 1994