ArticleNature communications2017
A general reaction mechanism for carbapenem hydrolysis by mononuclear and binuclear metallo-β-lactamases.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
What it found
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Who cites it
63 citing papers in PubMed, 121 citations in OpenAlex.
- The global epidemiology and treatment of metallo-β-lactamase-producing gram-negative pathogens.JAC-antimicrobial resistance · 2026Review
- Functional dynamics of water in New Delhi metallo-β-lactamase catalysis.Protein science : a publication of the Protein Society · 2026Article
- Genetic diversity, biochemical properties, epidemiology, and detection methods of IMP- and VIM-type carbapenemases.Clinical microbiology reviews · 2025Review
- OXA β-lactamases frommBio · 2025Article
- Mechanism of Ampicillin Hydrolysis by New Delhi Metallo-β-Lactamase 1: Insight From QM/MM MP2 Calculation.Journal of computational chemistry · 2025Article
- Biochemical properties and substrate specificity of GOB-38 in Elizabethkingia anophelis.Scientific reports · 2025Article
- OXA β-lactamases frombioRxiv : the preprint server for biology · 2024Article
- Antibiotics: From Mechanism of Action to Resistance and Beyond.Indian journal of microbiology · 2024Review
- Current Strategy for Targeting Metallo-β-Lactamase with Metal-Ion-Binding Inhibitors.Molecules (Basel, Switzerland) · 2024Review
- Attaching Metal-Containing Moieties to β-Lactam Antibiotics: The Case of Penicillin and Cephalosporin.Inorganic chemistry · 2024Article
- Rational Design of Benzobisheterocycle Metallo-β-Lactamase Inhibitors: A Tricyclic Scaffold Enhances Potency against Target Enzymes.Journal of medicinal chemistry · 2024Article
- Structural role of K224 in taniborbactam inhibition of NDM-1.Antimicrobial agents and chemotherapy · 2024Article
- Drug Discovery in the Field of β-Lactams: An Academic Perspective.Antibiotics (Basel, Switzerland) · 2024Review
- Taxifolin as a Metallo-β-Lactamase Inhibitor in Combination with Augmentin against Verona Imipenemase 2 ExpressingMicroorganisms · 2023Article
- Fifty years of biophysics in Argentina.Biophysical reviews · 2023Article
- Auranofin Targeting the NDM-1 Beta-Lactamase: Computational Insights into the Electronic Configuration and Quasi-Tetrahedral Coordination of Gold Ions.Pharmaceutics · 2023Article
- Unveiling the structural features that regulate carbapenem deacylation in KPC-2 through QM/MM and interpretable machine learning.Physical chemistry chemical physics : PCCP · 2023Article
- Structural insights into the substrate specificity of IMP-6 and IMP-1 metallo-β-lactamases.Journal of biochemistry · 2022Article
- Time-resolved β-lactam cleavage by L1 metallo-β-lactamase.Nature communications · 2022Article
- Recent Developments to Cope the Antibacterial Resistance via β-Lactamase Inhibition.Molecules (Basel, Switzerland) · 2022Review
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 5 countries.
Funding
Abstract
Carbapenem-resistant Enterobacteriaceae threaten human health, since carbapenems are last resort drugs for infections by such organisms. Metallo-β-lactamases (MβLs) are the main mechanism of resistance against carbapenems. Clinically approved inhibitors of MBLs are currently unavailable as design has been limited by the incomplete knowledge of their mechanism. Here, we report a biochemical and biophysical study of carbapenem hydrolysis by the B1 enzymes NDM-1 and BcII in the bi-Zn(II) form, the mono-Zn(II) B2 Sfh-I and the mono-Zn(II) B3 GOB-18. These MβLs hydrolyse carbapenems via a similar mechanism, with accumulation of the same anionic intermediates. We characterize the Michaelis complex formed by mono-Zn(II) enzymes, and we identify all intermediate species, enabling us to propose a chemical mechanism for mono and binuclear MβLs. This common mechanism open avenues for rationally designed inhibitors of all MβLs, notwithstanding the profound differences between these enzymes' active site structure, β-lactam specificity and metal content.Carbapenem-resistant bacteria pose a major health threat by expressing metallo-β-lactamases (MβLs), enzymes able to hydrolyse these life-saving drugs. Here the authors use biophysical and computational methods and show that different MβLs share the same reaction mechanism, suggesting new strategies for drug design.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.