9H14
Crystal structure of OXA-163 in complex with avibactam
This is a non-PDB format compatible entry.
Summary for 9H14
| Entry DOI | 10.2210/pdb9h14/pdb |
| Descriptor | Beta-lactamase, (2S,5R)-1-formyl-5-[(sulfooxy)amino]piperidine-2-carboxamide, (2S,5R)-1-methanoyl-5-(oxidanylamino)piperidine-2-carboxamide, ... (8 entities in total) |
| Functional Keywords | antibiotic resistance, beta lactamase, class d, dbo, antimicrobial protein |
| Biological source | Enterobacter cloacae More |
| Total number of polymer chains | 2 |
| Total formula weight | 57203.01 |
| Authors | Hoff, J.F.,Goudar, K.E.,Hinchliffe, P.,Spencer, J. (deposition date: 2024-10-09, release date: 2025-09-03, Last modification date: 2025-09-24) |
| Primary citation | Hoff, J.F.,Goudar, K.E.,Calvopina, K.,Beer, M.,Hinchliffe, P.,Shaw, J.M.,Tooke, C.L.,Takebayashi, Y.,Cadzow, A.F.,Harmer, N.J.,Mulholland, A.J.,Schofield, C.J.,Spencer, J. Electrostatic interactions influence diazabicyclooctane inhibitor potency against OXA-48-like beta-lactamases. Rsc Med Chem, 2025 Cited by PubMed Abstract: Carbapenemases, β-lactamases hydrolysing carbapenem antibiotics, challenge the treatment of multi-drug resistant bacteria. The OXA-48 carbapenemase is widely disseminated in , necessitating new treatments for producer strains. Diazabicyclooctane (DBO) inhibitors, including avibactam and nacubactam, act on a wide range of enzymes to overcome β-lactamase-mediated resistance. Here we describe investigations on how avibactam and nacubactam inhibit OXA-48 and two variants, OXA-163 and OXA-405, with deletions in the β5-β6 loop neighbouring the active site that modify activity towards different β-lactam classes. Nacubactam is ∼80-fold less potent than avibactam towards OXA-48, but this difference reduces in OXA-163 and OXA-405. Crystal structures and molecular dynamics simulations reveal electrostatic repulsion between Arg214 on the OXA-48 β5-β6 active-site loop and nacubactam, but not avibactam; effects absent from simulations of OXA-163 and OXA-405, which lack Arg214. Crystallographic and mass spectrometry data demonstrate that all three enzymes support desulfation of the bound DBOs. The results indicate that interactions with Arg214 affect DBO potency, suggesting that sequence variation in OXA-48-like β-lactamases affects reactivity towards inhibitors as well as β-lactam substrates. PubMed: 40927637DOI: 10.1039/d5md00512d PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.56 Å) |
Structure validation
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