ArticleBioorganic & medicinal chemistry2013
An altered zinc-binding site confers resistance to a covalent inactivator of New Delhi metallo-beta-lactamase-1 (NDM-1) discovered by high-throughput screening.
Article in Bioorganic & medicinal chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 41 citations in OpenAlex.
- Structure-activity relationship of captopril derivatives as New Delhi metallo beta-lactamase 1 inhibitors.ADMET & DMPK · 2026Review
- Elucidation of critical chemical moieties of metallo-β-lactamase inhibitors and prioritisation of target metallo-β-lactamases.Journal of enzyme inhibition and medicinal chemistry · 2024Review
- Rejuvenation of Meropenem by Conjugation with Tilapia Piscidin-4 Peptide Targeting NDM-1ACS omega · 2024Article
- Distinct Inhibition Modes of New Delhi Metallo-β-lactamase-1 Revealed by NMR Spectroscopy.JACS Au · 2023Article
- Enzyme Inhibitors: The Best Strategy to Tackle Superbug NDM-1 and Its Variants.International journal of molecular sciences · 2021Review
- Discovery and characterization of New Delhi metallo-β-lactamase-1 inhibitor peptides that potentiate meropenem-dependent killing of carbapenemase-producing Enterobacteriaceae.The Journal of antimicrobial chemotherapy · 2020Article
- A Lysine-Targeted Affinity Label for Serine-β-Lactamase Also Covalently Modifies New Delhi Metallo-β-lactamase-1 (NDM-1).Biochemistry · 2019Article
- NDM Metallo-β-Lactamases and Their Bacterial Producers in Health Care Settings.Clinical microbiology reviews · 2019Review
- Semi-rational screening of the inhibitors and β-lactam antibiotics against the New Delhi metallo-β-lactamase 1 (NDM-1) producingRSC advances · 2018Article
- Clinical Variants of New Delhi Metallo-β-Lactamase Are Evolving To Overcome Zinc Scarcity.ACS infectious diseases · 2017Article
- Discovery of novel new Delhi metallo-β-lactamases-1 inhibitors by multistep virtual screening.PloS one · 2015Article
- Real-time monitoring of New Delhi metallo-β-lactamase activity in living bacterial cells by 1H NMR spectroscopy.Angewandte Chemie (International ed. in English) · 2014Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Due to the global threat of antibiotic resistance mediated by New Delhi metallo-beta-lactamase-1 (NDM-1) and the lack of structurally diverse inhibitors reported for this enzyme, we developed screening and counter-screening assays for manual and automated formats. The manual assay is a trans-well absorbance-based endpoint assay in 96-well plates and has a Z' factor of 0.8. The automated assay is an epi-absorbance endpoint assay in 384-well plates, has a Z' factor of ≥0.8, good signal/baseline ratios (>3.8), and is likely scalable for high-throughput screening (HTS). A TEM-1-based counter-screen is also presented to eliminate false positives due to assay interference or off-target activities. A pilot screen of a pharmacologically characterized compound library identified two thiol-modifying compounds as authentic NDM-1 inhibitors: p-chloromecuribenzoate (p-CMB) and nitroprusside. Recombinant NDM-1 has one Cys residue that serves as a conserved active-site primary zinc ligand and is selectively modified by p-CMB as confirmed by LC-MS/MS. However a C208D mutation results in an enzyme that maintains almost full lactamase activity, yet is completely resistant to the inhibitor. These results predict that covalent targeting of the conserved active-site Cys residue may have drawbacks as a drug design strategy.
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