6ZGM
Crystal Structure of the VIM-2 Acquired Metallo-beta-Lactamase in Complex with the thiazolecarboxylate inhibitor ANT2681
Summary for 6ZGM
| Entry DOI | 10.2210/pdb6zgm/pdb |
| Descriptor | Metallo-beta-lactamase VIM-2-like protein, ZINC ION, ACETATE ION, ... (5 entities in total) |
| Functional Keywords | metallo-beta-lactamase, triazole-thione inhibitor, antibiotic resistance, carbapenem-hydrolyzing beta-lactamase, hydrolase |
| Biological source | Pseudomonas aeruginosa |
| Total number of polymer chains | 1 |
| Total formula weight | 26289.02 |
| Authors | Docquier, J.D.,Pozzi, C.,Marcoccia, F.,De Luca, F.,Benvenuti, M.,Mangani, S. (deposition date: 2020-06-19, release date: 2020-09-02, Last modification date: 2024-01-24) |
| Primary citation | Davies, D.T.,Leiris, S.,Sprynski, N.,Castandet, J.,Lozano, C.,Bousquet, J.,Zalacain, M.,Vasa, S.,Dasari, P.K.,Pattipati, R.,Vempala, N.,Gujjewar, S.,Godi, S.,Jallala, R.,Sathyap, R.R.,Darshanoju, N.A.,Ravu, V.R.,Juventhala, R.R.,Pottabathini, N.,Sharma, S.,Pothukanuri, S.,Holden, K.,Warn, P.,Marcoccia, F.,Benvenuti, M.,Pozzi, C.,Mangani, S.,Docquier, J.D.,Lemonnier, M.,Everett, M. ANT2681: SAR Studies Leading to the Identification of a Metallo-beta-lactamase Inhibitor with Potential for Clinical Use in Combination with Meropenem for the Treatment of Infections Caused by NDM-ProducingEnterobacteriaceae. Acs Infect Dis., 6:2419-2430, 2020 Cited by PubMed Abstract: The clinical effectiveness of the important β-lactam class of antibiotics is under threat by the emergence of resistance, mostly due to the production of acquired serine- (SBL) and metallo-β-lactamase (MBL) enzymes. To address this resistance issue, multiple β-lactam/β-lactamase inhibitor combinations have been successfully introduced into the clinic over the past several decades. However, all of those combinations contain SBL inhibitors and, as yet, there are no MBL inhibitors in clinical use. Consequently, there exists an unaddressed yet growing healthcare problem due to the rise in recent years of highly resistant strains which produce New Delhi metallo (NDM)-type metallo-carbapenemases. Previously, we reported the characterization of an advanced MBL inhibitor lead compound, ANT431. Herein, we discuss the completion of a lead optimization campaign culminating in the discovery of the preclinical candidate ANT2681, a potent NDM inhibitor with strong potential for clinical development. PubMed: 32786279DOI: 10.1021/acsinfecdis.0c00207 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.65 Å) |
Structure validation
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