6S1S
Crystal structure of AmpC from Pseudomonas aeruginosa in complex with [3-(2-carboxyvinyl)phenyl]boronic acid] inhibitor
Summary for 6S1S
| Entry DOI | 10.2210/pdb6s1s/pdb |
| Descriptor | Beta-lactamase, (~{E})-3-[3-(dihydroxyboranyl)phenyl]prop-2-enoic acid, PHOSPHATE ION, ... (4 entities in total) |
| Functional Keywords | inhibitor, complex, ampc, hydrolase |
| Biological source | Pseudomonas aeruginosa |
| Total number of polymer chains | 1 |
| Total formula weight | 43736.17 |
| Authors | Kekez, I.,Vicario, M.,Bellio, P.,Tosoni, E.,Celenza, G.,Blazquez, J.,Tondi, D.,Cendron, L. (deposition date: 2019-06-19, release date: 2019-10-09, Last modification date: 2024-10-09) |
| Primary citation | Linciano, P.,Vicario, M.,Kekez, I.,Bellio, P.,Celenza, G.,Martin-Blecua, I.,Blazquez, J.,Cendron, L.,Tondi, D. Phenylboronic Acids Probing Molecular Recognition against Class A and Class C beta-lactamases. Antibiotics, 8:-, 2019 Cited by PubMed Abstract: Worldwide dissemination of pathogens resistant to almost all available antibiotics represent a real problem preventing efficient treatment of infectious diseases. Among antimicrobial used in therapy, β-lactam antibiotics represent 40% thus playing a crucial role in the management of infections treatment. We report a small series of phenylboronic acids derivatives (BAs) active against class A carbapenemases KPC-2 and GES-5, and class C cephalosporinases AmpC. The inhibitory profile of our BAs against class A and C was investigated by means of molecular docking, enzyme kinetics and X-ray crystallography. We were interested in the mechanism of recognition among class A and class C to direct the design of broad serine β-Lactamases (SBLs) inhibitors. Molecular modeling calculations vs GES-5 and crystallographic studies vs AmpC reasoned, respectively, the ortho derivative and the meta derivative binding affinity. The ability of our BAs to protect β-lactams from BLs hydrolysis was determined in biological assays conducted against clinical strains: Fractional inhibitory concentration index (FICI) tests confirmed their ability to be synergic with β-lactams thus restoring susceptibility to meropenem. Considering the obtained results and the lack of cytotoxicity, our derivatives represent validated probe for the design of SBLs inhibitors. PubMed: 31574990DOI: 10.3390/antibiotics8040171 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.78 Å) |
Structure validation
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