Structural analysis of an "open" form of PBP1B from Streptococcus pneumoniae.
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.
Lovering
Andrew L
AL
Department of Biochemistry and Molecular Biology, Center for Blood Research, University of British Columbia, Vancouver, Canada.
De Castro
Liza
L
Lim
Daniel
D
Strynadka
Natalie C J
NC
D001426:Bacterial Proteins / Q000737:chemistry*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D015394:Molecular Structure; D046915:Penicillin-Binding Proteins / Q000737:chemistry*; D011487:Protein Conformation; D012694:Serine; D013296:Streptococcus pneumoniae / Q000737:chemistry*
D001426:Bacterial Proteins; D046915:Penicillin-Binding Proteins; D012694:Serine