9SG9
PENICILLIN-BINDING PROTEIN 1B (PBP-1B) IN COMPLEX WITH A MONOBACTAM (6)
This is a non-PDB format compatible entry.
Summary for 9SG9
| Entry DOI | 10.2210/pdb9sg9/pdb |
| Related | 9SG5 9SG6 9SG7 9SG8 9SGA 9SGB 9SGC 9SGD 9SGE |
| Descriptor | Penicillin-binding protein 1B, [(2~{S},3~{S})-3-[2-(3-hydroxyphenyl)ethanoylamino]-4-oxidanylidene-butan-2-yl]sulfamic acid, SULFITE ION, ... (5 entities in total) |
| Functional Keywords | cell wall, peptidoglycan synthesis enzyme, drug-binding protein, monobactam, transferase |
| Biological source | Streptococcus pneumoniae |
| Total number of polymer chains | 1 |
| Total formula weight | 55404.05 |
| Authors | |
| Primary citation | Kavas, V.,Contreras-Martel, C.,Pajk, S.,Knez, D.,Martins, A.,Gould, T.A.,Roper, D.I.,Zdovc, I.,Dessen, A.,Hrast Rambaher, M.,Gobec, S. Structure-Activity Relationship and Crystallographic Study of New Monobactams. J.Med.Chem., 2026 Cited by PubMed Abstract: Monobactams, a subclass of β-lactam antibiotics with a monocyclic scaffold, are uniquely resistant to hydrolysis by metallo-β-lactamases, providing a distinct therapeutic advantage. Here, we report an -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 , 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 , which is typically resistant to monobactams. 2D similarity search identified potent inhibitors active against , , and . 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. PubMed: 41632911DOI: 10.1021/acs.jmedchem.5c02427 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.88 Å) |
Structure validation
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