ReviewFrontiers in microbiology2018
Exploring Additional Dimensions of Complexity in Inhibitor Design for Serine β-Lactamases: Mechanistic and Intra- and Inter-molecular Chemistry Approaches.
Review in Frontiers in microbiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 32 citations in OpenAlex.
- Structural perspectives on clinical β-lactamase inhibitors: From mechanism to resistance.Journal of microbiology (Seoul, Korea) · 2026Review
- SAND: a comprehensive annotation of class D β-lactamases using structural alignment-based numbering.Antimicrobial agents and chemotherapy · 2025Article
- Distinct Inhibition Modes of New Delhi Metallo-β-lactamase-1 Revealed by NMR Spectroscopy.JACS Au · 2023Article
- Metagenomic Insights for Antimicrobial Resistance Surveillance in Soils with Different Land Uses in Brazil.Antibiotics (Basel, Switzerland) · 2023Article
- Analysis of a novel class A β-lactamase OKP-B-6 of Klebsiella quasipneumoniae: structural characterisation and interaction with commercially available drugs.Memorias do Instituto Oswaldo Cruz · 2022Article
- Enzyme Inhibitors: The Best Strategy to Tackle Superbug NDM-1 and Its Variants.International journal of molecular sciences · 2021Review
- β-Lactam antibiotic targets and resistance mechanisms: from covalent inhibitors to substrates.RSC medicinal chemistry · 2021Review
- Advances in Understanding of the Copper Homeostasis inInternational journal of molecular sciences · 2021Review
- Discovery of potential inhibitors against New Delhi metallo-β-lactamase-1 from natural compounds: in silico-based methods.Scientific reports · 2021Article
- Structural Basis and Binding Kinetics of Vaborbactam in Class A β-Lactamase Inhibition.Antimicrobial agents and chemotherapy · 2020Article
- Repurposing approved drugs on the pathway to novel therapies.Medicinal research reviews · 2020Review
- Identifying Ortholog Selective Fragment Molecules for Bacterial Glutaredoxins by NMR and Affinity Enhancement by Modification with an Acrylamide Warhead.Molecules (Basel, Switzerland) · 2019Article
- The Role of the Ω-Loop in Regulation of the Catalytic Activity of TEM-Type β-Lactamases.Biomolecules · 2019Review
- The latest advances in β-lactam/β-lactamase inhibitor combinations for the treatment of Gram-negative bacterial infections.Expert opinion on pharmacotherapy · 2019Review
- Bicyclic Boronate VNRX-5133 Inhibits Metallo- and Serine-β-Lactamases.Journal of medicinal chemistry · 2019Article
- Bridged Nucleic Acids Reloaded.Molecules (Basel, Switzerland) · 2019Review
- β-lactam/β-lactamase inhibitor combinations: an update.MedChemComm · 2018Review
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
As a bacterial resistance strategy, serine β-lactamases have evolved from cell wall synthesizing enzymes known as penicillin-binding proteins (PBP), by not only covalently binding β-lactam antibiotics but, also acquiring mechanisms of deacylating these antibiotics. This critical deacylation step leads to release of hydrolyzed and inactivated β-lactams, thereby providing resistance for the bacteria against these antibiotics targeting the cell wall. To combat β-lactamase-mediated antibiotic resistance, numerous β-lactamase inhibitors were developed that utilize various strategies to inactivate the β-lactamase. Most of these compounds are "mechanism-based" inhibitors that in some manner mimic the β-lactam substrate, having a carbonyl moiety and a negatively charged carboxyl or sulfate group. These compounds form a covalent adduct with the catalytic serine via an initial acylation step. To increase the life-time of the inhibitory covalent adduct intermediates, a remarkable array of different strategies was employed to improve inhibition potency. Such approaches include post-acylation intra- and intermolecular chemical rearrangements as well as affecting the deacylation water. These approaches transform the inhibitor design process from a 3-dimensional problem (i.e., XYZ coordinates) to one with additional dimensions of complexity as the reaction coordinate and time spent at each chemical state need to be taken into consideration. This review highlights the mechanistic intricacies of the design efforts of the β-lactamase inhibitors which so far have resulted in the development of "two generations" and 5 clinically available inhibitors.
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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.