29AI
Crystal structure of EcLpxC complexed with compound 7a
This is a non-PDB format compatible entry.
Summary for 29AI
| Entry DOI | 10.2210/pdb29ai/pdb |
| Descriptor | UDP-3-O-acyl-N-acetylglucosamine deacetylase, ZINC ION, 5-oxidanyl-4-[2-[4-[2-[4-[[(3-oxidanylcyclobutyl)amino]methyl]phenyl]ethynyl]phenyl]ethyl]-1~{H}-pyrimidin-6-one, ... (5 entities in total) |
| Functional Keywords | lpxc, metalloprotease, antibiotic, inhibitor |
| Biological source | Escherichia coli |
| Total number of polymer chains | 4 |
| Total formula weight | 132368.25 |
| Authors | Beaumont, E.,Cade, I.,Kopec, J.,Martin, D. (deposition date: 2026-03-03, release date: 2026-07-29, Last modification date: 2026-08-26) |
| Primary citation | Martin, D.P.,Teng, M.,Nammalwar, B.,Perez, C.,Li, X.,Munguia, J.,Taganov, K.,Fan, J.,Agarwalla, S.,Lonergan, D.,Tomaras, A.P.,Zimmerman, Z.,Puerta, D.T. Discovery and Optimization of Novel Nonhydroxamate LpxC Inhibitors for the Treatment of Multidrug-Resistant Gram-Negative Infections. J.Med.Chem., 69:18692-18704, 2026 Cited by PubMed Abstract: This report summarizes the discovery and optimization of a novel series of nonhydroxamate inhibitors targeting LpxC, a Zn2+-dependent hydrolase that is essential for the survival of Gram-negative bacteria. Beginning with a 5-hydroxypyrimidin-4-one metal-binding pharmacophore, structure-based approaches were utilized to generate a series of potent inhibitors that exhibited activity against a wide variety of Enterobacterales, including both susceptible and multidrug-resistant pathogens, and efficacy in murine thigh infection models. These novel compounds were evaluated in a rat model of cardiovascular toxicity to demonstrate the safety of the scaffold relative to another LpxC inhibitor that proved unsuccessful in Phase I clinical trials. A variety of inhibitors with potent in vivo efficacy and no hemodynamic effects were identified, which constituted an initial suite of potential development candidates. PubMed: 42593942DOI: 10.1021/acs.jmedchem.6c01036 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.618 Å) |
Structure validation
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