9sg9

PENICILLIN-BINDING PROTEIN 1B (PBP-1B) IN COMPLEX WITH A MONOBACTAM (6)

spinqualitylabelsall models 9sg9, resolution 1.88Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9sg9 is a 1 chain structure with sequence from Streptococcus pneumoniae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.88Å Ligands: A1JNW, CL, SO3 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function O70038_STREE Publication Abstract from PubMed Monobactams, a subclass of beta-lactam antibiotics with a monocyclic scaffold, are uniquely resistant to hydrolysis by metallo-beta-lactamases, providing a distinct therapeutic advantage. Here, we report an in silico-based structure-activity relationship (SAR) investigation of aztreonam-related monobactams. A focused library of monobactam derivatives was synthesized and evaluated for inhibition of penicillin-binding proteins (PBPs) and antibacterial activity. Ten compounds, including aztreonam, were crystallized with truncated PBP1b from Streptococcus pneumoniae, used as a model PBP. Potent PBP1b inhibitors were developed, although high enzymatic potency was not always reflected in strong antibacterial activity. Certain derivatives showed activity against Staphylococcus aureus, which is typically resistant to monobactams. 2D similarity search identified potent inhibitors active against Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii. Crystal structures revealed previously unrecognized binding interactions, including a halogen bond with a conserved threonine residue, underscoring the potential of these interactions to support the development of more potent PBP inhibitors. Structure-Activity Relationship and Crystallographic Study of New Monobactams.,Kavas V, Contreras-Martel C, Pajk S, Knez D, Martins A, Gould TA, Roper DI, Zdovc I, Dessen A, Hrast Rambaher M, Gobec S J Med Chem. 2026 Feb 3. doi: 10.1021/acs.jmedchem.5c02427. PMID:41632911 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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