7RPE
X-ray crystal structure of OXA-24/40 in complex with ertapenem
Summary for 7RPE
| Entry DOI | 10.2210/pdb7rpe/pdb |
| Descriptor | Beta-lactamase, (4R,5S)-3-({(3S,5S)-5-[(3-carboxyphenyl)carbamoyl]pyrrolidin-3-yl}sulfanyl)-5-[(1S,2R)-1-formyl-2-hydroxypropyl]-4-methyl-4,5-dihydro-1H-pyrrole-2-carboxylic acid, SULFATE ION, ... (5 entities in total) |
| Functional Keywords | acyl-enzyme complex, carbapenemase, hydrolase, hydrolase-inhibitor complex, hydrolase/inhibitor |
| Biological source | Acinetobacter baumannii |
| Total number of polymer chains | 1 |
| Total formula weight | 28448.53 |
| Authors | Powers, R.A.,Mitchell, J.M.,June, C.M. (deposition date: 2021-08-03, release date: 2022-07-06, Last modification date: 2023-11-15) |
| Primary citation | Mitchell, J.M.,June, C.M.,Baggett, V.L.,Lowe, B.C.,Ruble, J.F.,Bonomo, R.A.,Leonard, D.A.,Powers, R.A. Conformational flexibility in carbapenem hydrolysis drives substrate specificity of the class D carbapenemase OXA-24/40. J.Biol.Chem., 298:102127-102127, 2022 Cited by PubMed Abstract: The evolution of multidrug resistance in Acinetobacter spp. increases the risk of our best antibiotics losing their efficacy. From a clinical perspective, the carbapenem-hydrolyzing class D β-lactamase subfamily present in Acinetobacter spp. is particularly concerning because of its ability to confer resistance to carbapenems. The kinetic profiles of class D β-lactamases exhibit variability in carbapenem hydrolysis, suggesting functional differences. To better understand the structure-function relationship between the carbapenem-hydrolyzing class D β-lactamase OXA-24/40 found in Acinetobacter baumannii and carbapenem substrates, we analyzed steady-state kinetics with the carbapenem antibiotics meropenem and ertapenem and determined the structures of complexes of OXA-24/40 bound to imipenem, meropenem, doripenem, and ertapenem, as well as the expanded-spectrum cephalosporin cefotaxime, using X-ray crystallography. We show that OXA-24/40 exhibits a preference for ertapenem compared with meropenem, imipenem, and doripenem, with an increase in catalytic efficiency of up to fourfold. We suggest that superposition of the nine OXA-24/40 complexes will better inform future inhibitor design efforts by providing insight into the complicated and varying ways in which carbapenems are selected and bound by class D β-lactamases. PubMed: 35709986DOI: 10.1016/j.jbc.2022.102127 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.53 Å) |
Structure validation
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