6TD0
Crystal structure of vaborbactam bound to KPC-2
Summary for 6TD0
| Entry DOI | 10.2210/pdb6td0/pdb |
| Descriptor | Carbapenem-hydrolyzing beta-lactamase KPC, Vaborbactam, GLYCEROL, ... (5 entities in total) |
| Functional Keywords | inhibitor, boronate, beta-lactamase, antimicrobial protein |
| Biological source | Klebsiella pneumoniae |
| Total number of polymer chains | 1 |
| Total formula weight | 31768.27 |
| Authors | Tooke, C.L.,Hinchliffe, P.,Spencer, J. (deposition date: 2019-11-07, release date: 2020-01-22, Last modification date: 2024-11-13) |
| Primary citation | Tooke, C.L.,Hinchliffe, P.,Krajnc, A.,Mulholland, A.J.,Brem, J.,Schofield, C.J.,Spencer, J. Cyclic boronates as versatile scaffolds for KPC-2 beta-lactamase inhibition. Rsc Med Chem, 11:491-496, 2020 Cited by PubMed Abstract: carbapenemase-2 (KPC-2) is a serine-β-lactamase (SBL) capable of hydrolysing almost all β-lactam antibiotics. We compare KPC-2 inhibition by vaborbactam, a clinically-approved monocyclic boronate, and VNRX-5133 (taniborbactam), a bicyclic boronate in late-stage clinical development. Vaborbactam inhibition is slowly reversible, whereas taniborbactam has an off-rate indicating essentially irreversible complex formation and a 15-fold higher on-rate, although both potentiate β-lactam activity against KPC-2-expressing . High resolution X-ray crystal structures reveal closely related binding modes for both inhibitors to KPC-2, with differences apparent only in positioning of the endocyclic boronate ester oxygen. The results indicate the bicyclic boronate scaffold as both an efficient, long-lasting, KPC-2 inhibitor and capable of supporting further iterations that may improve potency against specific enzyme targets and pre-empt the emergence of inhibitor resistant KPC-2 variants. PubMed: 33479650DOI: 10.1039/c9md00557a PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (0.99 Å) |
Structure validation
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