ArticleProceedings of the National Academy of Sciences of the United States of America2021
Competing off-loading mechanisms of meropenem from an l,d-transpeptidase reduce antibiotic effectiveness.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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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
14 citing papers in PubMed, 20 citations in OpenAlex.
- The Novel Carbapenem, JDB/PQ-1-219, Has Potent Broad Spectrum Activity against Multi-Drug ResistantACS infectious diseases · 2026Article
- Peptide Mimetic Platform for Activity Profiling of Mycobacterial l,d-Transpeptidases.Biochemistry · 2026Article
- Activity Profiling of Mycobacterial L,D-Transpeptidases.bioRxiv : the preprint server for biology · 2026Article
- Comparative evaluation of five β-Lactamase inhibitors in combination with β-Lactams against multidrug-resistant Mycobacterium tuberculosis in vitro.BMC infectious diseases · 2025Article
- Decarboxylation of the Catalytic Lysine Residue by the C5α-Methyl-Substituted Carbapenem NA-1-157 Leads to Potent Inhibition of the OXA-58 Carbapenemase.ACS infectious diseases · 2024Article
- Measuring Interactions Between Proteins and Small Molecules or Nucleic Acids.Current protocols · 2024Review
- Restricted Rotational Flexibility of the C5α-Methyl-Substituted Carbapenem NA-1-157 Leads to Potent Inhibition of the GES-5 Carbapenemase.ACS infectious diseases · 2024Article
- Drug Discovery in the Field of β-Lactams: An Academic Perspective.Antibiotics (Basel, Switzerland) · 2024Review
- Review
- The implication of Mycobacterium tuberculosis-mediated metabolism of targeted xenobiotics.Nature reviews. Chemistry · 2023Review
- The l,d-Transpeptidase LdtACS infectious diseases · 2022Article
- Structure-Activity Relationship of Penem Antibiotic Side Chains Used against Mycobacteria Reveals Highly Active Compounds.ACS infectious diseases · 2022Article
- Article
- β-Lactam antibiotic targets and resistance mechanisms: from covalent inhibitors to substrates.RSC medicinal chemistry · 2021Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The carbapenem family of β-lactam antibiotics displays a remarkably broad spectrum of bactericidal activity, exemplified by meropenem's phase II clinical trial success in patients with pulmonary tuberculosis, a devastating disease for which β-lactam drugs historically have been notoriously ineffective. The discovery and validation of l,d-transpeptidases (Ldts) as critical drug targets of bacterial cell-wall biosynthesis, which are only potently inhibited by the carbapenem and penem structural classes, gave an enzymological basis for the effectiveness of the first antitubercular β-lactams. Decades of study have delineated mechanisms of β-lactam inhibition of their canonical targets, the penicillin-binding proteins; however, open questions remain regarding the mechanisms of Ldt inhibition that underlie programs in drug design, particularly the optimization of kinetic behavior and potency. We have investigated critical features of mycobacterial Ldt inhibition and demonstrate here that the covalent inhibitor meropenem undergoes both reversible reaction and nonhydrolytic off-loading reactions from the cysteine transpeptidase Ldt
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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.