2I72
AmpC beta-lactamase in complex with 5-diformylaminomethyl-benzo[b]thiophen-2-boronic acid
Summary for 2I72
| Entry DOI | 10.2210/pdb2i72/pdb |
| Related | 1CB3 1KE4 |
| Descriptor | Beta-lactamase, {5-[(DIFORMYLAMINO)METHYL]-1-BENZOTHIEN-2-YL}BORONIC ACID (3 entities in total) |
| Functional Keywords | ampc, beta-lactamase, cephalosporinase, serine hydrolase, hydrolase |
| Biological source | Escherichia coli |
| Cellular location | Periplasm: P00811 |
| Total number of polymer chains | 2 |
| Total formula weight | 79702.00 |
| Authors | Venturelli, A.,Cancian, L.,Tondi, D.,Morandi, F.,Cannazza, G.,Segatore, B.,Prati, F.,Amicosante, G.,Shoichet, B.K.,Costi, M.P. (deposition date: 2006-08-30, release date: 2007-09-11, Last modification date: 2024-10-30) |
| Primary citation | Venturelli, A.,Tondi, D.,Cancian, L.,Morandi, F.,Cannazza, G.,Segatore, B.,Prati, F.,Amicosante, G.,Shoichet, B.K.,Costi, M.P. Optimizing Cell Permeation of an Antibiotic Resistance Inhibitor for Improved Efficacy J.Med.Chem., 50:5644-5654, 2007 Cited by PubMed Abstract: Benzo[b]thiophene-2-ylboronic acid, 1, is a 27 nM inhibitor of the class C beta-lactamase AmpC and potentiates the activity of beta-lactam antibiotics in bacteria that express this and related enzymes. As is often true, the potency of compound 1 against the enzymes is much attenuated in cell culture against Gram negative bacteria, where the minimum inhibitor concentration of compound 1 is in the mid-micromolar range. Here, we modulated the properties of this lead to enhance its ability to cross the membrane, using a combination of X-ray crystallography, structure-based design, and application of physical models of outer membrane crossing. This strategy led us to derivatives with substantially improved permeability. Also, the greater solubility of these compounds allowed us to measure their efficacy at higher concentrations than with the lead 1, leading to higher maximum potentiation of the antibiotic effect of ceftazidime on resistant bacteria. PubMed: 17956081DOI: 10.1021/jm070643q PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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