7AU1
Structure of P. aeruginosa PBP3 in complex with a benzoxaborole (Compound 12)
Summary for 7AU1
| Entry DOI | 10.2210/pdb7au1/pdb |
| Related | 7ATM 7ATO 7ATW 7ATX 7AU0 7AU8 7AU9 7AUB 7AUH |
| Descriptor | Peptidoglycan D,D-transpeptidase FtsI, DIMETHYL SULFOXIDE, DI(HYDROXYETHYL)ETHER, ... (6 entities in total) |
| Functional Keywords | d, d-transpeptidase, boron-binding, divalency, hydrolase |
| Biological source | Pseudomonas aeruginosa |
| Total number of polymer chains | 1 |
| Total formula weight | 59330.29 |
| Authors | Newman, H.,Bellini, B.,Dowson, C.G. (deposition date: 2020-11-02, release date: 2021-08-11, Last modification date: 2024-10-16) |
| Primary citation | Newman, H.,Krajnc, A.,Bellini, D.,Eyermann, C.J.,Boyle, G.A.,Paterson, N.G.,McAuley, K.E.,Lesniak, R.,Gangar, M.,von Delft, F.,Brem, J.,Chibale, K.,Schofield, C.J.,Dowson, C.G. High-Throughput Crystallography Reveals Boron-Containing Inhibitors of a Penicillin-Binding Protein with Di- and Tricovalent Binding Modes. J.Med.Chem., 64:11379-11394, 2021 Cited by PubMed Abstract: The effectiveness of β-lactam antibiotics is increasingly compromised by β-lactamases. Boron-containing inhibitors are potent serine-β-lactamase inhibitors, but the interactions of boron-based compounds with the penicillin-binding protein (PBP) β-lactam targets have not been extensively studied. We used high-throughput X-ray crystallography to explore reactions of a boron-containing fragment set with the PBP3 (PaPBP3). Multiple crystal structures reveal that boronic acids react with PBPs to give tricovalently linked complexes bonded to Ser294, Ser349, and Lys484 of PaPBP3; benzoxaboroles react with PaPBP3 via reaction with two nucleophilic serines (Ser294 and Ser349) to give dicovalently linked complexes; and vaborbactam reacts to give a monocovalently linked complex. Modifications of the benzoxaborole scaffold resulted in a moderately potent inhibition of PaPBP3, though no antibacterial activity was observed. Overall, the results further evidence the potential for the development of new classes of boron-based antibiotics, which are not compromised by β-lactamase-driven resistance. PubMed: 34337941DOI: 10.1021/acs.jmedchem.1c00717 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.36 Å) |
Structure validation
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