All β-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 β-lactam-recognizing proteins, which includes the active-site serine β-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 Å resolution. The molecule has three domains, the central domain being a transpeptidase, which is a suitable target for antibiotic development.
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Pares, S., Mouz, N., Pétillot, Y. et al. X-ray structure of Streptococcus pneumoniae PBP2x, a primary penicillin target enzyme. Nat Struct Mol Biol 3, 284–289 (1996) doi:10.1038/nsb0396-284
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