Beyond structure and activity: targeting class A carbapenemases with monocyclic and bicyclic boronic acids to counter antimicrobial resistance
Bicyclic boronic acids inhibit SME-1 carbapenemase <i>via</i> a unique π-π stacking with His105 and covalent interaction with Ser70. Ledaborbactam shows the strongest inhibition, with the lowest <i>k</i><sub>i</sub> and enhanced structural stability. X-ray crystallography and molecular dynamics reveal key features helpful in structure-based optimization of boronates targeting class A β-lactamases.
Authors
- Saugata Hazra (ORCID: https://orcid.org/0000-0002-3074-1534)
- Narayan Chandra Mishra (ORCID: https://orcid.org/0000-0003-1546-3537)
- Mousumi Hazra (ORCID: https://orcid.org/0000-0001-5791-7993)
- Kunal Dhankhar (ORCID: https://orcid.org/0000-0002-1013-8746)
- Adwaita S. R. Nair (ORCID: https://orcid.org/0009-0009-0264-1833)
- Alaa Eddin Alhmeidi Alkhatib
Institutions
- Gurukul Kangri Vishwavidyalaya (IN)
- Indian Institute of Technology Roorkee (IN)
Publication Details
- Journal
- Organic & Biomolecular Chemistry
- Published
- 2025-11-04
- DOI
- https://doi.org/10.1039/d5ob01703c
- Primary Topic
- Antibiotic Resistance in Bacteria
- Type
- article
- Field-Weighted Citation Impact
- 0.00