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Structural analysis of an "open" form of PBP1B from Streptococcus pneumoniae

¹ Department of Biochemistry and Molecular Biology, and the Center for Blood Research, University of British Columbia, Vancouver V6T 1R9, Canada
² Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139, USA

(RECEIVED January 25, 2006; FINAL REVISION April 7, 2006; ACCEPTED April 10, 2006)

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 Å 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 -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: penicillin-binding protein; crystal structure; peptidoglycan; conformational change; transpeptidase

Article published online ahead of print. Article and publication date are at http://www.proteinscience.org/cgi/doi/10.1110/ps.062112106.

Abbreviations: ASU, asymmetric unit; EDTA, ethylenediaminetetraacetic acid; GT, glycosyltransferase; IPTG, isopropyl thio--d-galactoside; MRSA, methicillin-resistant Staphylococcus aureus; PEG MME, polyethylene glycol monomethyl ether; PBP, penicillin binding protein; TP, transpeptidase; RMSD, root mean square deviation.

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